text:
Direct electrochemical detection of individual collisions between magnetic microbead/silver nanoparticle conjugates and a magnetized ultramicroelectrode† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc02259b

Magnetic fields and silver nanoparticles increase the frequency and current signature of collisions between individual particles and electrode surfaces.

Introduction
In this paper, we report a new method for amplifying the current signature of collisions between single particles and electrode surfaces. 1 The specic approach we describe could evolve into a viable means for using single-particle collisions for low-level sensing applications: something that has not yet been achieved. The method involves direct electrochemical detection of silver nanoparticles (AgNPs) conjugated to conductive magnetic microbeads (cMmBs) via DNA hybridization. Detection limits as low as 20 aM are achieved due to two factors. First, the presence of multiple AgNPs on each cMmB, and, second, the ability of a magnetic ultramicroelectrode (UME) to increase the rate of mass transport of the cMmBs, relative to diffusion, to the UME surface. These results are signicant for the following three reasons. First, they demonstrate the feasibility of direct electrochemical detection of DNA-conjugated AgNPs, which can be used as labels for a variety of electrochemical assays. Second, we provide a detailed analysis of the parameters that control AgNP detection, which are relevant to future bioassays based on collisions. Third, we describe a simple method for preparing magnetic UMEs that will be useful for many different types of applications.
The experiment described in this article is set up as follows. First, as shown in Scheme 1a, the cMmBs are prepared by coating a magnetic microbead with Au to produce a conductive shell, and then this shell surface is modied with AgNPs using DNA hybridization to yield a conjugate of the form: cMmB-DNA-AgNP. Second, a magnetic UME is prepared by coating the surface of a Ni wire with a thin layer of Au, and then placing magnets around the wire to magnetize it (Scheme 1b). Third, as shown in Scheme 1c, an electrochemical cell is congured so that when the cMmB-DNA-AgNP composite is driven to the electrode surface by the magnetic eld, the associated AgNPs oxidize more or less simultaneously. This gives rise to an anodic current transient of the type shown in Scheme 1c.
This work was motivated principally by earlier reports from the groups of Lemay, 1 Compton, 2 and by one of our own prior studies. 3 Lemay and co-workers were the rst to describe electrochemical detection of collisions between individual nanoparticles and an electrode surface. Specically, they studied collisions between nonconductive latex beads, having diameters of 150 and 500 nm, and a 5 mm Au UME. 1 Upon striking the electrode surface, the latex particles were found to irreversibly adsorb to the surface of the UME, and this was signaled by a stepwise decrease in the faradaic current. The current is attenuated because each particle partially blocks the active surface area of the electrode, thereby hindering mass transport of a redox probe (ferrocenemethanol, FcMeOH). This work was extended by Bard and co-workers, who investigated the effect of low electrolyte concentration on collision frequency and amplitude of the current change via nite element simulations. 4 We further extended Lemay's ndings by correlating optical tracking and electrochemical measurements of collisions between insulated microbeads and a UME surface. 5 The collision trajectory was tracked using uorescence microbeads, and the highest current change was observed when the microbead struck or migrated to the edge of the UME. This nding is consistent with both theory and simulations that predict the highest current ux to be at the edges. 6 Additionally, Yoo et al. showed that it is possible to detect insulated magnetic microbeads (iMmB) in a microelectrochemical device at concentrations as low as 500 zM using a single, moveable magnet placed under the channel of the device. 3 Pre-enrichment steps collected the microbeads inside the channel inlet and then focused them at the working electrode.
The Compton 2,7-12 and Pumera 13 groups have described a different type of electrochemical collision experiment that is also highly relevant to the ndings reported here. In their work, individual or agglomerated metal nanoparticles, usually Ag, strike a UME surface resulting in a burst of anodic current. The important point about this type of approach is that the charge resulting from each collision can be directly correlated to the size of the colliding nanoparticle.

Results and discussion
Synthesis and characterization of conductive magnetic microbeads modied with AgNPs (cMmB-DNA-AgNP) As will be discussed later, it is not possible to carry out experiments like those reported here successfully using iMmBs. This is because the surface of the iMmB is not conductive, and therefore only the AgNPs within $1 nm of the electrode would be oxidized. As a result, only a tiny fraction of the total number of AgNPs dispersed on the surface of the iMmB would yield a signal, and assays built on the approach described here would be insufficiently sensitive to be worthwhile.
The procedure for preparing cMmBs is described in detail in the ESI † but is briey outlined here. 32 We start with commercially available iMmBs surface-functionalized with negatively charged carboxylate groups. These are mixed with AuNPs having positively charged 2-aminoethanethiol on their surface ( Fig. S1 and S2, ESI †). As shown by the micrographs in To ensure that most or all of the nanoparticles on the surface of the cMmB-DNA-AgNP conjugate are electrochemically addressable, we carried out the following experiment. The cMmB-DNA-AgNP beads were drop cast onto a glassy carbon electrode (GCE) congured in an electrochemical cell in a faceup orientation. Fig. 2 shows six consecutive ASVs obtained using a single electrode in a solution containing 100 mM NaCl and 10 mM phosphate buffer (pH 7, referred to hereaer as 100 mM PBCl). The black trace is the rst ASV, and it exhibits two Ag oxidation peaks: a large peak at $70 mV and a much smaller peak at $25 mV. It is worth noting, however, that the small peak at $25 mV is not present on every rst scan. The magnitude of the total charge under these two peaks is 3.37 mC, which corresponds to 6.77 Â 10 7 AgNPs. The shi in peak position for the second and subsequent scans will be discussed later.
To demonstrate the importance of the conductive Au shell in these studies, we carried out a control experiment using iMmBs (no conductive shell) functionalized with AgNPs. These materials were prepared by reacting streptavidin-coated MmB (sMmB, Fig. S4a †) with biotinylated DNA modied AgNPs. An SEM image of the resulting sMmB-DNA-AgNP conjugate is shown in Fig. S4b. † The important result is that when the experiment described in the previous paragraph is carried out using the sMmB-DNA-AgNP conjugate instead of that based on the conductive analog, no detectable ASV current is detected (Fig. S4c †). This conrms the necessity of rendering the iMmBs conductive prior to carrying out collision experiments.
To demonstrate that DNA hybridization is primarily responsible for attachment of cMmBs to AgNPs in the cMmB-DNA-AgNP conjugate, we carried out a control experiment in which noncomplementary DNA was used for the attachment link. ASVs for conjugates built using noncomplementary and complementary DNA are compared in Fig. 3a, and the integrated charge for the two resulting peaks is provided in Fig. 3b. The results clearly show that the average charge from the stripping peak is signicantly lower when noncomplementary DNA is used. In other words, there is only a very small amount of nonspecically adsorbed AgNPs on the cMmBs.
We return now to the second through sixth scans in Fig. 2. These result in just a single peak at $20 mV, which is the location of the rst small peak in the rst scan. For the following discussion we will refer to the peak at $20 mV as the rst peak and the one at $70 mV as the second peak. To understand the origin of these two peaks, the following experiments were performed using the procedure described earlier for the rst peak. First, when the potential of the GCE was held at 100 mV prior to returning it to the initial potential of À200 mV and then recording the ASV, the second peak did not appear. Second, when shorter DNA was used to link the cMmBs to the AgNPs, the second peak decreased in size and the rst peak increased. On the basis of these experiments, we believe that the origin of two peaks in the ASVs is related to the insulating DNA layer and the possibility that both AgCl and Ag + are  figure). At the conclusion of the individual scans, the electrode potential was stepped back to À0.20 V and held there for 3.0 s before the next scan was initiated. The electrolyte was 100 mM PBCl buffer. products of the electrooxidation of Ag. For the purposes of the present work this is not an especially important point, but it does direct us to hold the electrode potential more positive than the second ASV peak for the collision experiments. More information about the two peaks is provided in the ESI (Fig. S5-S7 †).
Fabrication of a magnetic Ni/Au UME The detection limit of electrochemical collision experiments is limited by the ux of particles to the electrode surface. 4,19,22 Normally, this ux is determined by diffusion, and because particles are large in comparison to molecules, their diffusion coefficients, the hence the limits of detection (LODs) of collision experiments, are generally not very low. To achieve lower LODs, diffusion must be supplemented by a second means of mass transfer like electrophoresis, 4 pressure-driven ow, 24,25 or, as in the present case, a magnetic force. [32][33][34][35][36][37] Note that attempts to use electrophoresis and pressure-driven ow to lower LODs have not been very successful.
There are a number of ways one might imagine integrating a magnet into an electrochemical cell for collision experiments. For example, a tiny permanent magnet could be located beneath a microfabricated UME, but this would be very difficult to implement. If the magnet was much larger than the UME, then MmBs would be trapped at locations other than the electrode surface. It is possible to fabricate very small electromagnets, but that is also experimentally challenging and in addition the heat resulting from the windings of the magnet introduces a new variable to the experiment. [38][39][40] To avoid these types of problems, we simply magnetized the UME itself using an external magnet that focuses the magnetic eld at the tip of the electrode.
The magnetic UME used here consists of a Ni wire with a thin layer of Au deposited on its tip using galvanic exchange. 41,42 Specically, a 50 mm Ni UME was prepared by sealing a Ni wire in a glass capillary. As shown in Scheme 2, the Ni UME was then sealed in an acrylic plate using epoxy glue. Next, the surface of the electrode was polished to remove excess epoxy. A thin layer of Au was added by submerging the electrode in a 10 mM HAuCl 4 solution for 10 s with gentle stirring. This results in spontaneous galvanic exchange between the Ni wire and Au 3+ in solution. At this point the electrode was washed with a copious amount of DI water and checked under an optical microscope (Fig. S8 †) to visually conrm Au deposition by a color change from gray to orange.
The Ni/Au UME resulting from this process was mounted face-up in an electrochemical cell (Scheme 2f). In some cases the electrode was magnetized using ring magnets placed around the UME as shown in the scheme and Fig. S9. † In other cases, the magnets were absent so that control experiments could be carried out. Using the Ni/Au UME (in the absence of the magnets) a cyclic voltammogram (CV) of the Au surface was recorded in 100 mM phosphate buffer solution (pH 7). The red trace in Fig. 4 reveals the characteristic peak potentials (E p ) associated with Au oxidation (E p ¼ $0.7 V) and oxide reduction (E p ¼ $0.3 V). This CV can be compared to the black trace in Fig. 4, which shows that these peaks are absent prior to Au galvanic exchange. One nal note: of course Ni is less noble than Au, and therefore one would expect peaks associated with Ni oxidation and reduction. Their absence is a consequence of the formation of an oxide of nickel resulting from air exposure. 43 Detection of collisions between cMmB-DNA-AgNP conjugates and a magnetic Ni/Au UME Fig. 5a shows representative chronoamperograms (i-t curves) for collisions between cMmB-DNA-AgNP conjugates and a Ni/ Au UME using a 100 mM PBCl buffer. This experiment was Scheme 2 Fig. 4 Cyclic voltammograms of a Ni UME before (black) and after (red) electroless deposition of Au. The scans started at À0.20 V, the scan rate was 100 mV s À1 , and the electrolyte was 100 mM phosphate buffer (pH 7). carried out by setting the potential of Ni/Au UME to 200 mV, which is positive of both the rst and second ASV peaks shown in Fig. 2. The black trace is a control experiment that was recorded in the absence of the cMmB-DNA-AgNP conjugate, and its shape is similar to that observed in previous collision experiments. 2 The decrease in the background current as a function of time may be due to blockage of the electrode resulting from progressive accumulation of trace contaminates from solution, or a reduction in activity of the Au UME due to electrodeposition of Ag. 3 The red and blue traces were recorded in solutions containing 100 aM of the cMmB-DNA-AgNP conjugate plus the PBCl buffer. The blue i-t trace was obtained in the presence of the magnetic eld, and it reveals numerous current transients associated with oxidation of AgNPs. When the magnets are removed from the electrode, the red i-t trace results. In this case, just a single, small current transient is observed. It is obvious that both the number and size of current transients are much larger when the magnetic eld is present. Fig. 5b and c are expanded views of the i-t data shown in Fig. 5a in the presence and absence of the magnetic eld, respectively. As mentioned earlier, the sharp current transients, which correspond to very fast oxidation of multiple AgNPs per cMmB, are much larger in the presence of the magnetic eld (Fig. 5b). Specically, the average charges for collisions in the presence and absence of the magnetic eld are 36.4 AE 33.7 pC and 8.5 AE 6.9 pC, respectively. Although one expects the collision frequency to increase in the presence of the eld (vide infra), it is not obvious that the magnitudes of the charges should differ so dramatically. We believe there are two possible explanations for this observation. First, the cMmB-DNA-AgNPs may aggregate in the presence of the magnetic eld, leading to larger current transients. 44 Second, it is possible that the cMmB-DNA-AgNPs are in better contact with the electrode or have a longer residence time on its surface in the presence of the eld.
The data in Fig. 5d were obtained by carrying out experiments like those described for Fig. 5a, but using concentrations of the cMmB-DNA-AgNP conjugate ranging from 20 to 200 aM. This plot of collision frequency vs. the conjugate concentration very clearly demonstrates that the magnetic eld enhances the rate of mass transfer of the MmBs to the electrode surface. Although it is difficult to draw a meaningful line through the data points obtained in the absence of the magnet, the ratio of the slopes of the best linear ts through the two sets of data is 4, suggesting that the magnet is responsible for a four-fold increase in signal.
The charge resulting from each collision in the presence of the magnetic eld was analyzed by measuring the area under the individual current transients as a function of the conjugate concentration (Fig. 6). Regardless of concentration, the majority of the charges range from 20 to 70 pC, with an overall average of 36.4 AE 33.7 pC. The latter value corresponds to oxidation of $732 AgNPs. 2 By measuring the concentration of the AgNPs before and aer incubation with the cMmBs (using the Nano-Sight particle counter), and taking into account the average diameter of the AgNPs (23.3 nm), we nd the average number of AgNPs per cMmB to be 3054 AE 260. This value is $4 times higher than the average measured from the collision data ($732 AgNPs). Although the agreement is actually pretty good, the differential is probably due to the different methods used for measurement. The value of 3054 AgNPs/cMmB should include all AgNPs, while the number measured using the collision data only takes into account those that are electrochemically accessible. Electrochemical inaccessibility could arise from AgNPs immobilized on patches of Au that are not in electrical contact with the electrode at the time of collision. Similarly, the presence of the DNA linkers could render some AgNPs too far from the surface of the cMmBs to be oxidized.
To determine if oxidation of the AgNPs is dependent on the potential applied to the Ni/Au UME, collision experiments were performed at three different potentials (Fig. 7). Fig. 7a shows representative i-t traces for these experiments. The blue, red, and black traces correspond to electrode potentials of À100, 0, and 200 mV, respectively. These three potentials were chosen because À100 mV is more negative than the Ag oxidation potential, 0 mV is at the onset of Ag oxidation, and 200 mV is well into the Ag oxidation potential. The black ASV in Fig. 7b was obtained by drop casting AgNPs onto a Au macroelectrode, and it shows the location of the Ag oxidation peak relative to these three potentials. It reveals a sharp anodic peak at $20 mV having an onset potential at $0 mV. Fig. 7b shows that the frequency of anodic current transients is signicantly higher at 200 mV compared to À100 and 0 mV (red data points). Additionally, the average charge for Ag oxidation is signicantly higher at 200 mV. These results are consistent with previous reports of naked AgNP collision experiments, which showed that the collision frequency and charge increase dramatically aer the onset potential for silver oxidation. 2

Summary and conclusions
In summary, we have described direct electrochemical detection of AgNPs linked to individual cMmBs. Importantly, the use of a magnetized Ni/Au UME increases the ux of this conjugate to the electrode surface, relative to diffusion, and therefore the collision frequency is higher. Moreover, for reasons we can only speculate on, the magnitude of the collisions is also greater in the presence of the eld. This has allowed detection of cMmB-DNA-AgNP conjugates down to a concentration of 20 aM, which corresponds to $61 fM AgNPs (recall there are $3000 AgNPs/ cMmB).
In addition to improving the limit of detection for collision experiments through the use of a magnetic eld, the other important aspect of this work is that the AgNP labels are linked to the cMmBs via DNA. That opens up the possibility of using collision experiments for DNA detection, which we are currently exploring as a possibility.   . 7 (a) i-t curves obtained for cMmB-DNA-AgNP conjugate collisions in the presence of a magnetic field. The concentration of cMmB-DNA-AgNP was 100 aM, and the potentials applied to the Ni/Au UME for each experiment are indicated in the legend. (b) Plot of frequency and charge vs. the applied potential. The black curve is a representative Ag stripping voltammogram obtained for AgNPs dropcast onto a Au macroelectrode (2 mm). The scan started at À0.2 V and ended at 0.3 V. The scan rate was 50 mV s À1 and the electrolyte was 100 mM PBCl buffer. The error bars were determined from three independent experiments at each potential.


extfieldsofstudy: Chemistry Medicine

text:
Synthesis of Phenolic Compounds by Trapping Arynes with a Hydroxy Surrogate

Trapping of arynes with various nucleophiles provides a range of heteroatom-functionalized arene derivatives, but the corresponding reaction with water does not provide phenol derivatives. Silver trifluroacetate (AgO2CCF3) can nicely solve this problem. It was found that in typical organic solvent, AgO2CCF3 readily reacts with arynes to generate trifluoroacetoxy organosilver arene intermediate, which, upon treating with silica gel, provides phenolic products. This protocol can be extended to the synthesis of α-halofunctionalized phenol derivatives by simply adding NBS (N-bromosuccinimides) or NIS (N-iodosuccinimides) to the reaction along with silver trifluroacetate, which provided α-bromo or α-iodophenol derivatives in good yield. However, the similar reactions with NCS (N-chlorosuccinimides) afforded only the protonated product instead of the expected α-chlorophenols derivatives. Interestingly, substrates containing silyl substituents on 1,3-diynes resulted in α-halotrifluoroacetates rather than their hydrolyzed product. Additionally, trapping the same arynes with other oxygen-based nucleophiles containing silver counter cation, along with NXS (N-halosuccinimides), generated α-halooxyfunctionalized products.

It would be highly desirable if we could expand the aryne trapping reaction to directly install a phenolic hydroxyl group on arene scaffolds, as this is an important functionality in large number of compounds, including natural products and pharmaceuticals [23,24]. In search of suitable reagents that can behave like a water surrogate under the given reaction conditions, we refer to a clue suggested by our previous nucleophile trapping study [21,25] of arynes, formed from various tetraynes (1), where nucleophiles (F − , F3C − , CF3S − ) associated with a silver counter cation, including silver trifluroacetate (AgO2CCF3), and provided excellent yields of the corresponding adducts (Scheme 1). Surprisingly, for the similar reaction with silver trifluoroacetate, the protonation of the initially formed putative intermediate 2 did not lead to the expected trifluoroacetate 3, instead, its deacetylated phenolic product 4 was obtained after purification [21]. Scheme 1. Trapping reactions of an in situ generated aryne intermediate with various nucleophiles with a silver counter cation.

Results and Discussion
On the basis of this initial observation, we carried out a systematic study of aryne trapping reactions with AgO2CCF3 as a water surrogate to prepare a variety of highly functionalized arene products containing a free phenolic hydroxyl group, and, herein, we report the results.
First, reactions with both symmetrical and unsymmetrical tetrayne substrates of varying substituents were screened to optimize conditions that produce formal water addition products (Table 1). It was quickly identified that the reaction with 1.5 equivalents of AgO2CCF3 in toluene at 90 °C, followed by purification on silica gel, afforded the phenolic products in good yields. Oxygen-tethered symmetrical tetrayne 1a with butyl substituents provided a mixture of ortho-and meta-OH adducts o-4a and m-4a in a 1.3:1 ratio (Entry 1). The reaction of all-carbon tethered substrate 1b with a gem-dicarboxylate moiety in place of the oxygen tether afforded a similar result, but with slightly improved selectivity and yield (87%) of o-4b and m-4b (Entry 2) [26]. Replacing the butyl groups with trimethylsilyl groups afforded only a single isomer o-4c (Entry 3) [21,[27][28][29][30][31][32][33][34][35][36][37]. Although the tether was also changed from oxygen in 1a to tosylated nitrogen in 1c, we believe this change has negligible impact on the selectivity. As expected, an ynamide-tethered unsymmetrical tetrayne with triethylsilyl substituents 1d afforded only the ortho isomer o-4d in 66% yield (Entry 4). A complete switch in regioselectivity was observed when a tosylated nitrogen tethered symmetrical bis-1,3-diyne with phenyl substituents was used, which provided in a majority m-4e along with o-4e in a 6.6:1 ratio (entry 5). This switch in regioselectivity can be explained in terms of the charge-controlled model [30], where the electron withdrawing phenyl group creates a more positive character on the farther carbon of the aryne. This allows the nucleophile to attack the meta carbon more preferably. This clearly indicates that, not the tether, but the substituents at the terminal carbon of the 1,3-diyne moieties are the main controlling elements for the selectivity [38]. With this result in hand, we envisioned that the putative organosilver intermediate 2 might be captured by suitable electrophiles to generate α-functionalized phenol derivatives. To test the viability of this hypothesis, the reaction was run with N-halosuccinimides under otherwise identical conditions, and the results are summarized in Table 2. When substrate 1a was treated with AgO2CCF3 (1.5 equiv.) and NBS (2.0 equiv.), a mixture of α-bromophenol derivatives o-5a-Br and m-5a-Br were obtained in 69% yield with a 1.6:1 ratio (Entry 1). Similarly, with NIS instead of NBS, the corresponding α-iodophenol derivatives o-5a-I and m-5a-I were isolated in 67% yield with a 1.8:1 ratio (Entry 2). Substrate 1b furnished the bromophenol derivatives in 63% yield with an expected selectivity of 1.4:1 [26]. N-Tosylamide tethered substrate 1f containing n-hexyl substituents provided bromo and iodophenol derivatives o-5f-Br/m-5f-Br and o-5a-I/m-5a-I in 83% and 88% yield with a 1.8 and 2.6 ratio, respectively (Entries 5 and 6). Tetrayne 1e containing phenyl substituents was found to be less efficient and provided a mixture of o-5e-Br and m-5e-Br in only 36% yield (Entry 4).
While exploring the scope of the direct synthesis of α-halophenol derivatives, we found that the silyl substituent ortho to the trifluoroacetate moiety interferes with its hydrolysis when halogen was incorporated. Thus, the reaction of 1g afforded single regioisomer o-6g-CF 3 as a major product along with expected phenolic product o-5g-Br in 10% yield (Entry 1) ( Table 3). This is in stark contrast to the formation of o-4c and o-4d, which are derived from their precursors via complete hydrolysis of the corresponding trifluoroacetates. Based on this observation, we further explored the 1,2-oxyhalogenation to form oxygen-masked form of halophenol derivatives ( Table 3). The reaction of substrate 1c in the presence of silver acetate and NBS provided single regioisomer o-6c-CH 3 along with phenolic product o-5c-Br in a 1:2.2 ratio (Entry 2). Unexpectedly, however, the reaction of 1c with AgO2CCF3 and NIS afforded a mixture of iodotrifluoroacetates o-6c and m-6c in a 6.2:1 ratio devoid of hydrolyzed product (Entry 3). Substrates 1a and 1f upon treating with silver triflate and NBS afforded a mixture of bromotriflates o-6a/m-6a (2.6:1) and o-6f/m-6f (4.8:1) in 82% and 94% yield, respectively (Entries 4 and 5) [39]. The reaction of 1f with silver benzoate and NBS provided a mixture of α-bromobenzoates o-6f-Br and m-6f-Br in 30% yield with a 2:1 ratio (Entry 6), but, with NCS, not even traces of the expected chloride-trapped product were obtained, instead only protonated products o-6f-H and m-6f-H were isolated in 76% yield with a 2.1:1 ratio (Entry 7).

General Information
Reactions were carried out in oven-dried glassware unless otherwise noted. Compounds were purchased from Aldrich, Acros, TCI America, or Oakwood Chemicals, unless otherwise noted. Toluene, acetonitrile, and dichloromethane were distilled over calcium hydride (CaH2) under a nitrogen atmosphere. THF was distilled over sodium-benzophenone ketyl under a nitrogen atmosphere. Column chromatography was performed using silica gel 60 Å (32−63 mesh), purchased from Silicycle Inc. (Quebec, QC, Canada). Analytical thin layer chromatography (TLC) was performed on 0.25 mm E. Merck precoated silica gel 60 (particle size 0.040−0.063 mm). Yields refer to chromatographically and spectroscopically pure compounds unless otherwise stated. 1 H-NMR and 13 C-NMR spectra were recorded on a Bruker AV-500 spectrometer (Bruker BioSpin Corporation, Billerica, MA, USA). 19 F-NMR spectrum was recorded in Varian Mercury-Vx-300 spectrometer (Palo Alto, CA, USA). 1 H-NMR chemical shifts (δ) are reported in parts per million (ppm) downfield of TMS and are referenced relative to the residual proteated solvent peak (CDCl3 (7.26 ppm)). 13 C chemical shifts (δ) are reported in parts per million downfield of TMS and are referenced to the carbon resonance of the solvent (CDCl3 (77.2 ppm)). Multiplicities are indicated by s (singlet), d (doublet), t (triplet), q (quartet), quin (quintet), sext (sextet), or m (multiplet). 1 H-NMR signals that fall within a ca. 0.3-ppm range are generally reported as a multiplet, with a range of chemical shift values corresponding to the peak or center of the peak. Coupling constants, J, are reported in Hz (Hertz). Electrospray ionization (ESI) mass spectra were recorded on a Waters Micromass Q-Tof Ultima (Waters Corporation, Milford, MA, USA) at the University of Illinois at Urbana-Champaign. Electron impact (EI) mass spectra and Chemical Ionization (CI) mass spectra were obtained using a Micromass 70-VSE (Waters Corporation, Milford, MA, USA) at the University of Illinois at Urbana-Champaign.

General Procedure for the Mono-Functionalization (GPM)
In a glove box, a mixture of a substrate (0.1 mmol, 1.0 equiv.) and a nucleophile (0.15 mmol, 1.5 equiv.) in dry toluene (3 mL) was taken into a Schlenk tube. The reaction mixture was stirred at 90 °C for 5 h, unless otherwise noted. After completion, the reaction mixture was transferred to a round-bottom flask, concentrated and loaded on silica gel column for chromatographic purification, using ethyl acetate-hexane mixture as the eluent.

Conclusions
In conclusion, we developed a formal hydration method of arynes generated from hexadehydro Diels-Alder reaction. While direct use of water does not efficiently trap the in situ generated arynes to generate phenolic products, silver trifluroacetate (AgO2CCF3) can behave as an effective water surrogate in these reactions. This is probably due to the improved miscibility and reactivity of AgO2CCF3 with arynes, compared to water, to generate the corresponding trifluoroacetoxy organosilver arene intermediates, and, upon treating, with silica gel, these intermediates readily undergo protonolysis of their carbon-silver bonds and hydrolysis of the trifluoroacetyl groups. This protocol can be extended to the synthesis of α-halofunctionalized phenol derivatives by simply adding NBS or NIS to the reaction along with silver trifluroacetate, which provided α-bromo or α-iodophenol derivatives in good yield. Interestingly, the similar reactions with NCS afforded only the corresponding protonated products instead of the expected α-chlorophenols derivatives. Unexpectedly, reactions of substrates containing trialkylsilyl substituents on 1,3-diynes provided α-halotrifluoroacetates rather than their hydrolyzed products. Trapping the same arynes with other oxygen-based nucleophiles containing a silver counter cation, along with NXS, generated α-halooxyfunctionalized products in good yields.

Acknowledgments
Financial support from UIC (LAS AFS) and the National Science Foundation (CHE 1361620) is greatly acknowledged. We are grateful to Furong Sun of the University of Illinois at Urbana-Champaign for high resolution mass spectrometry data.

Author Contributions
D.L. designed the research and wrote the paper. R.K. and S.G. performed the bench work for synthesizing starting materials and products. Everyone contributed to the analysis of the spectra. Y.X. carried out the computational study. All authors read and approved the final manuscript.

Conflicts of Interest
The authors declare no conflict of interest.


extfieldsofstudy:
Materials Science
Medicine

text:
Synthesis of Helical Carbon Fibers and Related Materials: A Review on the Past and Recent Developments

Helical carbon fibers (HCFs) have been widely studied due to their unique helical morphology and superior properties, which make them efficient materials for several potential applications. This review summarizes the past and current advancement on the synthesis of HCFs. The review focuses and discusses synthesis strategies and effect of experimental parameters on the growth of HCFs. The effect of preparation method of catalyst, catalyst nature, catalyst composition, catalyst size, catalyst initial and final shape, reaction temperature, reaction time, carbon source, impurities, and electromagnetic field on the growth of HCFs is reviewed. We also discuss the growth mechanism for HCFs and the synthesis of HCFs related materials. Finally, we conclude with a brief summary and an outlook on the challenges and future prospects of HCFs.

During the last decade, HCFs-based materials such as metal particles decorated HCFs, and composites of HCFs have also been extensively synthesized and studied for their potential applications in the fields of electrocatalyst [74,75], catalyst for hydrogen storage materials [72,76], sensors [77], electromagnetic wave absorbers [78], etc. The synthesis, properties and possible potential applications of HCFs have been reviewed by some researchers [16,79,80]. The aim of this review article is to elaborate the brief history and recent advancement on the synthesis of HCFs and related materials. We briefly cover the synthesis methodology and the effect of experimental parameters on the growth of HCFs.

Synthesis of Helical Carbon Fibers (HCFs)
A variety of methods have been explored for the synthesis of planar CFs such as arc discharge, laser vaporization and CVD. Among various preparation processes, CVD has been found to be the most efficient method for the synthesis of HCFs [60,81,82]. Mostly planar CFs have been obtained as a final product while using arc discharge and laser vaporization methods for the synthesis of carbon materials owing to their high synthesis temperature (>2000 °C) [83]. Vaporization of solid graphite for CFs growth require high growth temperature since carbon atoms gets higher mobility and results nearly perfect hexagonal graphite for the growth of planar CFs [83]. Conversely, carbon atoms get lower mobility in CVD method since, generally, the synthesis temperature is in the range of 400-1000 °C. The lower mobility of carbon atoms favors the formation of non-hexagonal graphite in the growing nucleus; and results a poor crystalline graphitic structure and formation of HCFs [83]. In addition to this, CVD provides easy control on the experimental parameters, which control the CFs growth [84,85]. However, except CVD, HCFs have also been synthesized using arc discharge [86], flame synthesis [87], and hydrothermal synthesis [88]. It should be emphasized here that the arc discharge, laser vaporization, and electrospinning, which are usually used in the synthesis of planar CFs, are generally not suitable for the preparation of HCFs. Since, reproducibility and yield of HCFs in these methods is low compared to CVD process and also these methods are costly compared to CVD. Table 1 shows the growth conditions for the synthesis of HCFs used by various researchers.

Chemical Vapor Deposition (CVD)
CVD is a chemical process in which catalyst and or substrate is exposed to one or more volatile precursors. By reactions or decomposition of precursors on catalyst/substrate surface, high quality, high-performance, solid materials can be produced. Till now, several CVD-based methods have been developed to produce high performance materials.

Catalytic Thermal CVD (CTCVD)
Catalytic thermal CVD (CTCVD) process involves the pyrolysis of a hydrocarbon (e.g., methane, acetylene, ethylene, etc.) over transition metals (e.g., Fe, Co, Ni, etc.) as catalysts at high temperatures (500-1000 °C) to produce carbon nanomaterials. Most of the researchers have been used CTCVD process for the growth and finding the optimal condition for HCFs on a large scale. CTCVD method was first used by Motojima et al. in the early 1990 to synthesize regularly coiled carbon filaments by Ni-catalyzed pyrolysis of acetylene containing a small amount of thiophene as an impurity at temperature of 350-750 °C [7,17]. In this study, Motojima et al. found that these regularly CFs consist of pair-coiled fibers, and were elastically extended up to about three times of the original coil length [17]. The carbon coils were grown perpendicularly, pointing in the direction of the source gas inlet, on the graphite substrate as shown in Figure 4 [7]. Here, a fine Ni grain material was used as catalyst and always observed on the tip of all the carbon coils (arrows in Figure 4). The regular carbon coils have a coil diameter of 3-6 µm, coil pitch of 0.5-0.7 µm without any coil gap, and coil length of 5-8 mm for a 2 h reaction time. The growth rate of the CFs that formed the carbon coils was about 7 µm/s and that of the carbon coils was 1 µm/s [7]. Zhang et al. synthesized carbon nanocoils (CNCs) in high yield, using iron-coated indium tin oxide as a catalyst and acetylene as a carbon source [101]. They obtained high yield of coils at deposition temperature of 700 °C; and found that the indium, tin, oxygen, and/or their alloys were decisive for the formation of coils. Yang et al. prepared carbon microcoils (CMCs) with changing coiling chirality using fine powders of WS2 and stainless steel plate as catalyst by CTCVD method [89]. Qin et al. prepared amorphous HCNFs with absolutely symmetric structures by polymerization (about 90%) and decomposition (about 10%) of acetylene over copper tartrate as acatalyst [102]. The reaction was carried out at low temperature of about 250 °C and gave good reproducibility and yield. They noticed that there were always two coiled CFs (CCFs) grown on a single copper nanocrystal. Interestingly, these two CCFs were identical in fiber diameter, coil diameter, coil pitch, coil length, and cycle number; however, they had opposite helical senses. CNCs have been synthesized using catalytic pyrolysis of acetylene in the temperature range of 740-770 °C [8]. Here, two conditions such as sputtered thin films of Au and Au/Ni were used as catalyst and a magnetic field was applied to the synthesis region of CNCs. Coil-in-coil CNCs have been synthesized by means of acetylene decomposition over nickel nanoparticles as catalysts [50]. In this study, CNCs self-assembled in one nanospring and the yield of CNCs was 11 g in each run at the synthesis temperature of 450 °C [50].

Microwave CVD
The functional materials can be prepared at lower temperatures and for shorter times with improved properties using microwave CVD method. The main advantageous feature of this method is that there is no need for impurity element in reaction zone for the synthesis of HCFs [90]. Xie et al. adopted a new approach to synthesize the micro CCFs using microwave CVD method [90]. In this study, they used a silicon carbide substrate since SiC absorbs microwaves very efficiently; and they did not use any toxic impurity gas as a growth promoter for HCFs. Their microwave system was composed of a switching power supply, which drives a 3kW magnetron, a circulator, stub-tuner, and a single mode cavity. The micro CCFs obtained by the microwave method was highly coiled and disordered (amorphous).

Hot Filament CVD
HCFs have been synthesized by a hot filament assisted CVD at a substrate temperature of 600 °C using cobalt and copper alloy films as catalyst [73]. In this study, the catalysts were prepared by thermal evaporation coating of a thin layer (20 nm) of cobalt and copper (Co:Cu = 5:1 by weight) on a SiO2/Si(110) (thermally oxidized, 1 µm thick SiO2) wafer. The metals were simultaneously evaporated with a tantalum boat filament in 2 × 10 −7 Torr pressure. After coating with metal layers, the substrates were introduced to the CVD system and heated to 600 °C in argon ambient. The heating rate was 100 °C/15 min and annealing of the substrates was carried out for 1 h. When the annealing process was completed, the filament (W, diameter = 0.5 mm) was heated to a temperature of 2000 °C, and 5% methane with argon was introduced to the system for 1 h. After completion of the synthesis, the samples were allowed to cool to room temperature while argon flowed through the system.

Arc Discharge
Zhang et al. synthesized carbon coils by decomposition of acetylene using arc discharge method under different gas pressures from 160 to 460 Torr over a metal plate [86]. They mentioned the advantageous feature of their method is that there is no need for the complex preparation of the catalyst particles and the introduction of the impurities. Their experimental apparatus is composed of a spectral pure graphite rod as an anode, a metal plate as cathode, acetylene as carbon source, reaction chamber, vacuum pump, circulatory system, DC power supply, etc. At a voltage of 35-40 V and an output current of 96 A, an arc was generated in an acetylene atmosphere and at a pressure of 160-460 Torr. After three minutes, the club-shaped products of sizes approximately 1 mm, deposited vertically over the surfaces of the plate.

Purification of HCFs
Mostly the as-synthesized HCFs contained metal catalyst particles as impurities, causing problems in property characterization as well as applications of HCFs. Purification of HCFs were usually a tough, lengthy, costly, and destructive process, and introduces defects into the purified sample [91]. However, in some cases, the presence of metal catalysts makes the as-synthesized HCFs advantageous in some fields such as catalyst, catalyst support, electromagnetic wave absorption, etc. Mostly acid treatment was applied for the purification of HCFs. Jaybhaye et al. removed amorphous carbon and metal particles from the as-synthesized spiral CNFs using acid treatment [45]. For removing impurities, the as-synthesized material was soaked in either conc. HNO3 or conc. HCl for 3 h. Then the material was washed with water till neutral pH. Finally, to remove the residual water, the sample was rinsed with acetone and then heated in an oven at 150 °C. Then the purified sample was heated up to 700 °C in hydrogen atmosphere for 2 h to oxidize the amorphous carbon [45]. Therefore, they obtained the purified spiral CNFs. For removing copper nanoparticles (Cu NPs), Li and Xu soaked their CNF samples in concentrated HNO3 acid for 1 h, separated by centrifugation, and washed with deionized water until the pH of the filtrate was neutral [67]. Further, the sample was washed with absolute ethanol and dried at 80 °C and purified sample were obtained. In order to avoid the complicated purification process of the as-synthesized material, Qi et al. used water-soluble salts NaNO3 as catalyst for the synthesis of high-purity linear and helical CNFs [91]. Since NaNO3 is water-soluble, it was removed from the as-synthesized materials through a washing process with deionized water, and high-purity HCNFs were obtained easily and undamaged. Ding et al. also used water-soluble Na2CO3 powder as catalyst for the synthesis of nitrogen-doped (N-doped) CNFs (N-CNFs) and N-doped CNCs (N-CNCs) at 450 and 500 °C, respectively [82]. Due to water-soluble property of NaCO3, through repeated washing with water and ethanol, there is complete elimination of Na2CO3 as well as ethanol-soluble organic impurity, and the products were obtained in high purity.

Effect of Experimental Parameters on the Growth of HCFs
Experimental parameters such as nature of catalyst [73,103], composition of catalyst [104], particle size of catalyst [68], type of carbon source [7], flow rate of gases [55], pressure of gases [86], synthesis temperature [67,85], and active shape (final shape) of the catalysts during synthesis [72,105], are the key parameters, which establish the growth process, structural morphology and microstructure of the as-synthesized HCFs.

Effect of Preparation of the Catalysts for the Growth of HCFs
Several researchers have been prepared special type of catalysts for synthesizing HCFs by adopting several techniques. These techniques include addition of additives or mixture of metal catalysts, use of a support, pretreatment of catalyst in a particular environment, using catalyst precursor, etc. These techniques may have considerable effects on carbon deposition, and HCFs with high relevant characteristic can be obtained using special type of catalysts. However, preparation of special type of catalysts is sometimes quite complicated and long process. Qin et al. prepared copper tartrate catalyst precursor by the slow addition of 50 mL of 0.1 M copper dichloride aqueous solution to 50 mL of 0.1 M sodium-potassium tartrate aqueous solution under vigorous stirring [61]. After that, nanocopper catalysts were obtained using thermal decomposition of copper tartrate at 250 °C. The nature and grain sizes of these Cu NPs were crystalline and about 50 nm, respectively. They successfully synthesized regularly CCNFs using these nanocoppersas catalysts. In another study of Tang et al., Fe nanoparticles have been prepared by the combined sol-gel/reduction method [57]. These nanoparticles were used as catalyst and effective for the growth of HCNFs at 450 °C . In comparison to the common Fe particles, the Fe nanoparticles prepared in such a way were decisive for the growth of HCNFs. In this study, there was no need to modify the Fe nanoparticles by any chiral reagent. The as-synthesized HCNFs were crystalline and symmetric, and (110) plane of the Fe particle was the mirror plane ( Figure 5). They also observed that compared to HCNFs obtained over nonmagnetic transition metals, samples containing magnetic Fe nanoparticles show higher magnetization. Recently, Jian et al. prepared CCFs from Ni nanoparticles using catalytic pyrolysis of acetylene [62]. In this study, they found that, one of the crucial factors to obtain high-purity CCFs is the controllable synthesis of catalyst nanoparticles. By controlling the reaction temperature and NaOH concentration, they prepared controllable Ni nanoparticles using liquid phase reduction of nickel sulfate with hydrazine hydrate. They used a surfactant polyvinylpyrrolidone (PVP) to prevent agglomeration of Ni nanoparticles. In another study, Jian et al. controlled the as-synthesized CFs into linear CNFs; and carbon coils including single-helix CNCs (SH-CNCs), single-helix CMCs (SH-CMCs), and twinning double-helix CMCs (TDH-CMCs) [55]. In this study, these various morphologies of CFs were prepared by only changing the N2 gas flow rate and all other experimental parameters were unchanged. Li and Xu prepared Cu NPs generated from the in situ decomposition of copper acetylacetonate [67]. These Cu NPs have been used for the selective synthesis of HCNFs, planar CNFs, CNTs, and nitrogen doped (N-doped) CNFs by adjusting the reaction temperatures or composition of feedstock gas.

Effect of Various Types of Catalysts on the Growth of HCFs
The properties of a nanostructure catalyst influence the CVD synthesis of CNFs [106]. Here, we discuss the effect of various types of catalysts on the growth of HCFs, which has been used by other researchers.

Effect of Transition Metals
Motojima et al. used a Ni single crystal plate (10 × 10 × 0.5 mm 3 ) as a catalyst for the growth of HCFs [107]. They examined the effect of respective crystal faces of Ni catalysts on coil yield. They observed that coil yield differed based on the crystal faces, the highest coil yield, in order, by Ni (100) > (111) > (110). Qin et al. synthesized amorphous HCNFs at very low temperature of 468 K (195 °C) using copper nanocrystal as a catalyst and acetylene as a gas source at normal pressure [92]. These nanocoils exhibit a symmetric growth mode in the form of twin helices. The majority of the angles between the two twin helices are about 70° or 110°. The IR, XRD, Raman, and C/H molar ratio revealed that HCNFs have a polymer-like structure with a weak trans-polyacetylene feature. These helical fibers were a mixture of solid polymers from acetylene coupling and a small amount of carbon from acetylene decomposition [92]. Nitze et al. synthesized HCNFs from CVD process at temperature of 550 °C, using C60 supported Pd nanoparticles as catalyst and acetylene as carbon feedstock [93]. Here, C60 molecules provided a support for separating Pd into nanoparticles. From the shape of catalyst particles and by adopting a simple model, they concluded that the straight nanofibers curl due to blocked carbon diffusion pathways on the catalyst particles.

Effect of Metal Carbides
Motojima et al. analyzed phase of the active catalyst for the growth of HCFs using X-ray diffraction (XRD) and electron diffraction pattern [108]. They found that Ni3C single crystal phase was decisive for the growth of HCFs, where thiophene was used as impurity gas. Further, Motojima et al. examined catalytic effect of various metals such as Ni, Mo, Zr, Ti, etc., on the growth of HCFs during the pyrolysis of acetylene [107]. In this study, the presence of corresponding metal carbides was identified by XRD analysis in the metal grain which was located at the tip of HCFs. Metal, sulfur and carbon were presented in the active catalyst and it was confirmed by electron probe microanalysis (EPMA). However, the corresponding metal sulfide phases were not detected by the XRD analysis. Accordingly, Motojima et al. suggested that the metal carbide phase containing solid solution of sulfur and metal, is the actual catalyst for coiling of CFs [107].

Effect of Mixture and Alloys of Metals
Pan et al. investigated the effect of combination of Fe and indium tin oxide (ITO) on the growth of CNCs [58]. They found that Fe and ITO are very important catalysts in the growth of CNCs. But neither Fe nor ITO can lead to the synthesis of CNCs separately. They found that Fe was essential for the growth of carbon nanotubules, whereas ITO induces their helical growth. In this study, the yield of CNCs was determined by the elemental ratio of tin and indium in the ITO film. Pan et al. further examined that the growing point of carbon coils was the interface of ITO and Fe films where catalyst particles are formed [81]. Okazaki et al. developed powder catalysts containing oxides of iron, indium, and tin (Fe-In-Sn-O) for the mass production of CNCs using a coprecipitation technique; and these powder catalysts were found to have the same ability as Fe/ITO thin film catalysts to grow CNCs [104]. They found that Fe was required to grow CNCs and fibers. However, Fe2O3 by itself could not grow both CNCs and fibers, due to the size of Fe2O3 particles produced in this study. It was found that Sn was required to grow CNCs, and the composition of Sn should be small to grow CNCs in high yield. On the other hand, indium increased the yield of CNCs by adjusting the crystalline sizes of Fe2O3 and SnO2 [104]. Yu et al. prepared Cu-Ni alloy nanoparticles by hydrogen arc plasma method [71]. They synthesized regular CCNFs with asymmetric growth mode by catalytic decomposition of acetylene using these Cu-Ni alloy nanoparticles as a catalyst at 241 °C [71]. Jayatissa and Guo synthesized CNTs using Co catalysts [73]. Furthermore, they obtained carbon helixes when the catalysts were changed to Co + Cu. In this study, the formation of carbon helixes is exclusively governed by the addition of Cu into Co catalysts. Au and K metals were used as bi-catalyst to assist thermal decomposition of C2H2 for the growth of CNCs [54]. In this investigation, Au and K were deposited on graphite foils substrates and studied the different reaction parameters on the formation of CNCs. Here, no carbon nanostructures (CNSs) were grown without the presence of K. On the other hand, featureless C layers were obtained in the reactions using K and substrates only. In contrast, CNSs in the form of nanoparticles, nanowires and nanocoils were obtained using both Au and K deposited on the substrates. Here, K worked as dehydrogenation catalysts to assist deposition of C from C2H2; and Au as nucleation seeds for the growth of CNSs.

Effect of Supported Catalyst
The substrate/supporter provide good dispersion of catalysts, higher activity, and selectivity towards the growth of CFs. Chen et al. prepared single-helix CNCs with various laces patterns on the surface by catalytic pyrolysis of acetylene using Ni metal catalyst supported on molecular sieve [109]. Molecular sieve contained a small amount of Fe impurity and was originated from a raw material of kaolin clay. They found that a trace amount of Fe impurity contained in the molecular sieve was a key factor for the lace growth. It was considered that Fe impurity may poison or restrain the formation of three crystals faces resulting in the growth of single helix coils, and also activates the anisotropic catalytic activity. Here, they also considered that a very strong inner stress is periodically formed between the boundary of two fibers, and thin carbon films may swell to form laces. In the investigation of Ren et al. Cu was used as catalyst over different supporters such as SiO2, TiO2, Al2O3, and MgO for the synthesis of HCNFs at relatively low temperature of 237 °C [94]. Mostly HCNFs were obtained using MgO as support compared to other three kinds of supports, and by decreasing the ratio of Cu/MgO, the content of HCNFs increases. The optimal results were obtained at the ratio of 1:10. Their investigation also showed that straight or curved CNFs were obtained using Cu catalyst without any support. Jian et al. used two types of substrate for the synthesis of CCFs such as graphite and ceramic plate [62]. In this study, although other reaction conditions were unchanged, they obtained regular CCFs with coil diameter of 3 µm and irregular CCFs with diameter of 1 µm, using graphite and ceramic plate as a substrate, respectively. The distortion of helical fiber occurred randomly, indicating that the interaction between catalyst and ceramic substrate differs from graphite substrate. Park and Kim synthesized carbon coils using acetylene as carbon source and SF6 as an incorporated additive gas by CTCVD method [110]. In this study, the supporting substrates were pretreated using various methods before carbon coils deposition reaction. Here, the exclusive formations of the nanosized carbon coils were obtained using thermal etching pretreatment of Ni-SiO2 substrate with SF6. In addition to this, diamond powders pretreatment of Si substrate gives rise to dominant formation of microsized carbon coils after 10 minutes reaction time.

Effect of Catalyst Particle Size on the Growth of HCFs
Only a few studies provide reasonable explanations to the relationship between the initial catalyst particle size and the diameter of CFs. Since particle size has a direct influence on CF diameter, so CF diameter can be modified by changing particle size. Recently, Wang et al. synthesized Cu nanoparticles with narrow size distribution by reduction of CuO films produced by atomic layer deposition (ALD), which are used as catalysts for the catalytic growth of CNSs [68]. By proper adjustment of ALD cycle numbers, the size of produced Cu nanoparticles was well controlled. They mentioned that Cu nanoparticles can be obtained by reduction of CuO films in hydrogen (5% H2/N2) atmosphere. However, in this synthesis, the CuO nanoparticle films are directly used as catalysts for the growth of CNCs without the hydrogen reduction step since acetylene undergoes slight decomposition at high temperature, leading to the release of reducing hydrogen. Uniform CNCs with nearly 100% purity were obtained using 50-80 nm Cu nanoparticles, while thin straight fibers and thick straight fibers were produced by applying 5-35 and 100-200 nm Cu nanoparticles, respectively [68].

Effect of Shape Changes and Final Shape of Catalyst Particles on the Growth of HCFs
In several studies, the initial shapes of catalyst particles were irregular, and after the growth, the shape of catalyst particles on the tip of HCFs is faceted, specific and regular. It suggests that some changes in the shape of catalyst particles must have take place during the growth process. In addition to this, not only the shape change, but due to the particle agglomeration phenomena and the phenomena of minimum energy, the sizes of catalyst particles also change during the growth process [62]. Kawaguchi et al. found that diamond-like or polyhedral-shaped catalyst particles were decisive for the growth of CCFs [97]. These CCFs were formed by the crossing or intertwining of the two primary coils, which were grown in the same coiling direction. The active catalyst particles were mainly composed of a Ni metal with polyhedral-shaped and were always observed on the tip of CCFs. Pan et al. found that the diameter, pitch, and shape of a carbon coil are related with the catalyst particle at its tip [81]. In addition to this, the shape of catalyst grain also determines the cross-section of CF [13]. Chen et al. observed that the cubic-shaped catalyst grains were decisive for the growth of circular coils and slender-shaped rhombus hexahedron catalyst grains were decisive for the growth of flat coils [13]. The shape changes of catalyst particles during HCFs growth were clearly seen in the study of Qin et al. [111]. They synthesized HCNFs with a symmetric growth mode by decomposition of acetylene over copper catalyst. In this study, single copper nanocrystals were decisive for the growth of two symmetrically helical fibers. They explained that upon contacting the initial copper nanocrystals with irregular shapes, acetylene began to decompose to form two straight fibers with the irregular tips. At the same time, the irregular tip of copper nanocrystals began to change to regular shape. After transformation of irregular to a regular faceted shape, the two straight CFs ceased to grow and two regular HCFs with opposite helical senses began to grow. If the regular faceted nanocrystals continue to changes shapes during fiber growth, the two helical fibers possibly changed into opposite helical senses, and thus give helical reversals. The shape changes were caused by the changes in surface energy resulting from the acetylene-adsorption on copper nanocrystals [111]. CMCs have been successfully prepared using catalytic decomposition of acetylene over nickel foam as catalyst at temperature of 973-1073 K [95]. In this study, thiophene was used as a growth promoter. The average initial grain size of Ni in the nickel foam was 5 µm, whereas the fibers diameter of the as-synthesized CMCs was 400-500 nm. Here, it was observed that catalyst particles at the tip of CMCs were 400 nm in size and rhombohedral in shape. This reveals that the sizes and shapes of catalyst particles undergo a transformation during the reaction time or CFs growth. AB5 type hydrogen storage material such as LaNi5 alloy has been used as catalyst precursor for the synthesis of HCNFs [72]. During the reaction course, the oxidative dissociation of LaNi5 (sizes ~6 µm) occurred and Ni particles (sizes ~1 µm) were produced. By the interaction with C2H2 and H2, Ni particles were fragmented to Ni nanoparticles (sizes ~150 nm) and by the surface reconstruction phenomena it adopted polygonal shape. At temperature of 650 °C, the growth of HCNFs was achieved through these polygonal shapes Ni nanoparticles. So in this study, the final shapes of the active catalyst particles were polygonal for the growth of HCNFs. However, the starting catalyst particles of LaNi5 alloy were irregular and bigger in size.

Effects of Reaction Temperature on the Growth of HCFs
Reaction temperatures strongly affect the anisotropy of catalyst grain, and thus morphologies and dimensions of carbon coils [60].

Morphology of HCFs
Liu and Shen used activated CNTs (ACNTs) supported Ni as catalyst to prepare HCFs, since ACNTs have a larger BET surface area and modified surface to support Ni catalyst [96]. In this study, effect of synthesis temperature on the morphology of final products was investigated within the range of 650-800 °C. Here, for loading of Ni catalyst, ACNTs were impregnated in Ni(NO3)2· 6H2O ethanol solution followed by sonication for 30 min. The mass ratio of Ni to ACNTs was 1:10. Accordingly the Ni containing ACNTs were obtained. They obtained irregular double CMCs, regular double CMCs, double and single CMCs, and CNCs at 800, 750, 700 and 650 °C, respectively, using ACNTs supported by Ni as catalyst. HCNFs have been synthesized using cupric tartrate as catalyst and temperature was below 500 °C by CVD method [38]. Here, effect of reaction temperature on the morphology of reaction products was studied. At low temperature of 280, 380 and 480 °C, planar CFs, HCNFs, and thin HCNFs was the main product, respectively. Raghubanshi et al. studied the effect of reaction temperature on the growth of HCNFs [72]. They used LaNi5 alloy as catalyst precursor and C2H2 as carbon source for the growth of HCNFs. They found that polygonal and spherical shapes of Ni nanoparticles were produced and decisive for the growth of HCNFs and planar CNFs at temperature of 650 and 750 °C, respectively.

Coil and Fiber Diameter of HCFs
Chen and Motojima observed that the coil and fiber diameter of HCFs were significantly affected by the reaction temperatures [112]. They prepared HCFs by Ni-catalytic pyrolysis of acetylene containing a small amount of thiophene, and investigated the effect of reaction temperature on the coil diameter of HCFs [60]. They found that the diameter of HCFs strongly depends on the reaction temperature. The regular carbon coil with small coil diameter (6-8 µm) were grown at temperature of 750 °C; and carbon coils with larger coil diameter (12-14 µm) and slightly irregular forms were grown at temperature of 820 °C ( Figure 6). Qin et al. observed that the coil diameters of coiled fibers were sensitive to reaction temperature, and could be changed from 100 nm to 10 µm by increasing the reaction temperature [61]. Liu and Shen also observed that diameters of carbon coil decreases while reducing the reaction temperature [96].

Yield of HCFs
Kawaguchi et al. investigated the effect of reaction temperature on the yield of HCFs [113]. In this study, HCFs were grown in a relatively narrow temperature range of 600 to 800 °C, while the planar CFs were grown in a wide temperature range of 400 to 1000 °C. The maximum yield (about 30 wt.%) of HCFs was obtained at about 700 °C. No deposition was observed at a temperature below 300 °C. On the other hand, only carbon powder (acetylene black) was obtained above 1000 °C. Ding et al. observed that when reaction temperature was higher than 500 °C or lower than 400 °C, the yield of N-doped CNCs (N-CNCs) was small for their experimental conditions [82]. Above 500 °C, Na2CO3 (catalyst) decomposes heavily into sodium oxide and CO2, this situation is unfavorable for the formation of carbon materials. Also below 400 °C, the decomposition of acetylene becomes adverse [82]. Tang et al. used 25 mg, 51 mg, and 163 mg, NiO as catalyst precursor for the synthesis of CNCs at temperature of 415, 425, 450 °C, respectively [50]. They obtained the yield of CNCs was 3.032, 2.41, and 11 g, respectively. So there is a significant increase in the yield of each run upon using a larger quantity of catalyst at higher temperature.

Effect of Type of Carbon Source on the Growth of HCFs
Most researchers have used acetylene (C2H2) as carbon feedstock for the growth of HCFs [7,38,56,62]. However, many carbon sources other than C2H2, such as methane (CH4), ethane (C2H6), propane (C3H8) [114], ethylene (C2H4), propylene (C3H6), carbon monoxide (CO), acetone [9], etc., have also been used as the carbon source for the growth of HCFs. However, when using hydrocarbons other than acetylene, HCFs were rarely obtained under any reaction conditions [114]. Chen and Motojima prepared HCFs using Ni catalyzed pyrolysis of propane, which was pre-heated at high temperatures, and examined the effects of preheating conditions on the growth of HCFs [114]. In this study, they observed that the growth of HCFs occurred via catalytic pyrolysis of acetylene, which was formed by pre-heating and pre-pyrolyzing of propane. Hence, they concluded that propane can be used as the carbon source for obtaining HCFs if it is pre-heated and pre-pyrolyzed at 1000-1100 °C to form acetylene. The as-synthesized HCFs were mostly irregular double coils with a large coil pitch of 1-5 µm and coil diameter of 5-40 µm [114].

Effect of Reaction Time on the Growth of HCFs
Chen and Motojima investigated the effect of reaction time on the morphology of HCFs [112]. In this study, different morphologies and coiling patterns of HCFs were obtained at different reaction times under standard conditions (Figure 7). It was observed that the clear tips or heads of the carbon coils were formed during 5-10 min period, but the body part had not been regularly formed. Carbon coils increased in coil length with increasing reaction time. Finally, the regular carbon coils were obtained for 2 h or more reaction time. Chen et al. observed that the circular carbon coils are usually formed during the initial growth stage and then gradually changes to the flat coils with increasing reaction time in an electromagnetic field [10].

Effect of Impurity Gas on the Growth of HCFs
Several researchers concluded that the presence of impurity in the reaction atmosphere is indispensable for the growth of HCFs. Kawaguchi et al. investigated the effect of impurity gas on the growth of CCFs [113]. In this study, HCFs were rarely obtained using high purity acetylene, but were obtained in high yield using commercially dissolved acetylene. They mentioned that commercially dissolved acetylene contains a small amount of (CH3)2CO, H2S, PH3, etc. as an impurity. They found that some of these impurities play an important role in the growth of HCFs. In these impurities, only hydrogen sulfide (H2S) showed a strong positive effect. For the favorable growth of CCFs, the optimum concentration of H2S in acetylene was 0.06-0.08 vol%. Excessive amounts of impurity may act as a poison on Ni catalyst. Kawaguchi et al. analyzed the electron diffraction pattern of the seeds, which were responsible for the growth of CCFs. They found that the seed is a Ni alloy such as a solid solution of Ni and carbon, which also contains small amounts of sulfur impurities. Thus, Kawaguchi et al. concluded that a small amount of sulfur impurity acts as an activation agent for a Ni catalyst for the growth of HCFs [113]. Motojima et al. examined the effects of various sulfur compounds, such as hydrogen sulfide, thiophene, n-butylmercaptane, dibenzylsulfide, etc., as impurities on the growth of CCFs [9]. Among the various sulfur compounds, they found that thiophene was the most effective for the growth of CCFs with a constant coil pitch and high yield. In this study, they also investigated the effect of phosphorus trichloride (PCl3) as an impurity on the growth of CCFs [9]. They found that a PCl3 impurity significantly accelerates the growth of CCFs. In another study, Chen et al. found that no CMCs were formed without sulfur promoter under their preparation conditions [95]. The reason can be explained on the basis of Kim et al. [115] consideration, that the presence of sulfur facilitated the catalyst abruption and increased the surface diffusion rate of metal atoms; so by the surface reconstruction phenomena the faceted metal crystallites are formed. It was also suggested that the impurity elements may dissolve into the metal catalyst and cause anisotropic catalytic behavior and thus the formation of CCFs achieved. To avoid the introduction of toxic and unpleasant compound like thiophene, PCl3, or H2S, etc., during the reaction condition and getting the thin film of quasi-aligned CMCs, Ni-sulfide were used as a catalyst by Mukhopadhyay et al. [97]. They mentioned that the ball milled Ni-sulfide particles had already the catalytic anisotropy which makes it decisive for the growth of CMCs at 740 °C.

Effect of External Electromagnetic (EM) Field and Bias Voltage on the Growth of HCFs
In-Hwang et al. examined the effect of external EM field and bias voltage on the growth of carbon coils [116]. EM field and bias voltage were applied to the reaction tube and substrate, respectively, and significantly affects the growth of carbon coils. Yield of carbon coils with an external EM field and bias voltage were 1.9-2.0 times higher than that obtained without an EM field and bias voltage [116]. In addition to this, morphology of carbon coils was also changed using external EM field and bias voltage. Kuzuya et al. examined the superimposed irradiation effects of EM field (AC, DC) emitted from both the outer and inner sides of the reaction tube on the growth, morphology and some properties of carbon coils [11]. Kuzuya et al. found that the coil yield increased by 1.1-1.2 times with superimposed application of AC or DC, EM field. Also, the density of the carbon coils increased with the application of EM field.

Synthesis of HCFs-Based Materials
Electroless deposition has been utilized for the uniform coatings of Ni-Fe-Co-P on CCNFs [78]. In this method, continuous coatings on CCNFs were achieved through proper pretreatments, surfactant and ultrasonic agitation. They found that in comparison with the uncoated CCNFs, the coated ones were fine ferromagnetic materials. In addition to this, the coated CCNFs have shown fine electromagnetic wave-absorbing property in the frequency region of 8-18 GHz [78]. Ding et al. synthesized N-doped CNCs (N-CNCs) using acetylene as carbon source at 500 °C. In this study, ammonia was used as a source of nitrogen and Na2CO3 powder as catalyst [82]. Their XRD results showed the decline of graphite signal intensity in CNCs after doping with nitrogen. The reinforcement of rubber has been performed by mixing of HCNFs in natural rubber (NR) [38]. In this study, addition of 100 wt.% HCNFs in NR provides the maximum bound-rubber content (37%). Here, the responsible factor for the amount of bound rubber is the unique coil structure of HCNFs. Jia et al. prepared Pd-HCNF nanocomposites by a one-step reduction free method in dimethylformamide (DMF) and applied in hydrogen peroxide and glucose detection [77]. Here, they prepared HCNFs using Pd2C60 as catalyst in a CVD system followed by functionalization with Pd nanoparticles. TEM image of HCNFs with diameter in the range of 40-60 nm is shown in Figure 8a. Individual Pd nanoparticles appear on the surface of HCNFs, after co-incubation with Pd2DBA3 in DMF (Figure 8b). Pd nanoparticles are highly dispersed and well anchored on HCNFs. The sizes of Pd nanoparticles are about 5 nm. The HRTEM image (inset in Figure 8b) shows lattice fringes of both graphitic sheets of HCNFs and Pd nanoparticles.

Growth Mechanism of HCFs
Growth mechanism of HCFs is very interesting. In the growth of HCFs, the rate-determining step is the diffusion of carbon through metal catalyst. In this regard, "anisotropy of carbon deposition" theory, which was proposed in 1992 by Kawaguchi et al. [113] for the growth of HCF and further confirmed in 1999 [7], has been the most accepted. In addition to this, many researchers have proposed numerous growth models for HCFs. Some of them are discuss here. Kawaguchi et al. proposed a growth mechanism for the pair-HCFs called the "quasi-VLS mechanism", which involves the surface diffusion of carbon species on Ni compound seed [113]. They observed that Ni compound seed located on the tip of coil fibers is the exclusive growing point and different crystal planes of this Ni compound seed have different catalytic abilities for the growth of HCFs. The opposite planes (X-X, Y-Y) in Ni compound seed are equivalent crystallographically, whereas adjacent planes (X-Y) are not equivalent (Figure 9Aa). According to this theory, initially, a Ni compound seed is formed by the reaction of a Ni particle with acetylene and impurity gas (H2S). The decomposition of acetylene were achieved through the catalytic ability of Ni compound seed and then two CFs were start to grow in a direction opposite from each pair of planes (X + Y) of Ni compound seed (Figure 9Ab). At this stage, due to the different growth rate of each plane, CFs twisted with a curvature corresponding to the diameter of coils. The coil diameter may depend not only on the difference in the growth rate of CFs, but also on the flexibility of CFs. Kawaguchi et al. considered that during the growth of CCFs, the surface of Ni compound seed should be in a liquid-like state (quasi-liquid), so that carbon atoms can diffuse rapidly on the surface of the seed and maintain a rapid growth of CCFs. Therefore, Kawaguchi et al. proposed that the driving force of the curling of a CF to form HCF is the anisotropic deposition rate of carbon on the respective crystal planes of a catalyst grain. Further, Chen and Motojima explained that the Ni catalyst seed is composed of Ni3C single crystals on the surface of which small amounts of sulfur and oxygen are contained [112]. They suggested that the different content of carbon, sulfur and oxygen on the respective crystal faces is the key factor for the anisotropic characteristics of the different crystal planes. Motojima and Chen proposed a three dimensional growth mechanism for CMCs according to the growth patterns and morphologies of carbon coils ( Figure 10) [7]. Figure 10A shows a carbon coil obtained during the initial growth stage. The coil diameters increased from about 15 µm at the tip part to 35 µm at the foot. The arrow in Figure 10(A&B) indicates a Ni catalyst grain. This Ni grain is an exclusive growing point for carbon coils. The postulated form of the Ni grain embedded into the node of the six fibers is shown in Figure 10C, in which the Ni grain is shown by a dashed cubic form outline, a-h. In this model, the order of the catalytic activity for the carbon deposition among the three crystal faces is A > B > C ( Figure 10D). Basically, a CF is formed from the fine carbon grains deposited from the three crystal faces of A, B, and C, and curl in such a way that the carbon grains deposited from the crystal faces A and B are on the outer surface of the coil, while the grains deposited from the crystal face C are inside surface. The anisotropy of the carbon deposition between the crystal faces of A and C, and/or B and C determines the coil diameters; while the coil pitch by that of A and B ( Figure 10D). According to this mechanism, the micro coiling morphology is formed by the rotation of a Ni catalyst grain, from which six fibers grow and coalescence together, followed by the formation of two fibers. These two fibers curl in the same direction around the coil axis and at the same speed of about one cycle per second ( Figure 10). Wen and Shen given the 3D growth model for coiled CNFs and coiled CNTs [59]. Their experimental results on CNFs were reasonably in good agreement with the "anisotropy of carbon deposition" theory. In this study, the crystal grain was a Ni-P-Cl co-crystal since they were added to a small amount of PCl3 into the acetylene gas [59]. In this model, Wen and Shen assumed that a fiber growing out of three contiguous crystal planes, (1,0,0), (0,1,0), and (0,0,1) with increasing carbon condensation rates, R(0,0,1) > R(0,1,0) > R(1,0,0); according to this rate the final shape of the CF was coiled ( Figure 11). The three adjacent crystal planes are labeled in different shades, with the darker one i.e., (0,0,1) having a higher fiber growth rate. The resultant fibers grown towards the crystal planes having the lower fiber growth rates i.e., (1,0,0), and so coiled shape forms. Amelinckx et al. proposed a formation mechanism for a catalytically grown helix-shaped graphite nanotube from a catalyst particle based on a spatial velocity hodograph [18]. Blank and Kulnitskiy proposed a formation mechanism for helically coiled CNFs from a catalyst of octahedral shape [117]. In this mechanism, the sp 3 bonded carbon atoms, surface tension force, and component of surface tension force played the role for curling the CNFs. Bandaru et al. proposed a plausible model for coiling in nanostructure growth motivated by both energy and entropic principles, that for a given volume of material, the helical form occupies the least amount of space [118].
Zhang et al. described the formation of carbon coils by giving some external module in addition to the anisotropy of the catalyst grain [86]. In this model, at first, the formation of straight CFs from catalyst particle and generation of van der Waals forces take place. Then, van der Waals force decreases due to change of temperature, and the distortion of fibers arises due to the stress along the fiber axis. Further, the elastic module of the straight fibers mainly controls the coil diameter, coil length, and coil pitch. Finally, angular momentum conservation is the governing factor for the two coils, which derive from the same catalyst grains, and have opposite helix.

Challenges and Future Prospects
HCFs are still commercially unavailable materials. Synthesis of high reproducibility of HCFs is a tedious task and remains a challenge due to low controllability of experimental parameters. Initially, some researchers were occasionally observed the growth of HCFs during the vapor phase preparation of CFs [51]. The growth of HCFs was generally accidental, in a very low yield and poorly reproducible. Thus, the controllable, reliable, and efficient synthesis of high purity HCFs is of key importance for scientific and industrial applications. In regard to this, a lot of work was carried out for the synthesis of HCFs with high yield and reproducibility [7,17,60]. However, mostly the growth of HCFs required the presence of either large or small amounts of toxic sulfur or phosphorus impurities in the conventional methods. So there is also a challenge to remove these hazardous materials from the synthesis technique of HCFs and provide a green and clean method. Because of the unique helical shape, HCFs have many potential applications such as catalyst, catalyst support, electromagnetic wave absorption material, electronic or electromagnetic nano-devices like in a Micro-Electro Mechanical System (MEMS) [12]. HCFs and their related materials may be applied as the absorbers of cosmic rays, for tunable micro-devices, micro-sensors, the formation of crosslink in nanocomposites, an actuator, activation catalysts for microorganisms, active molds for the preparation of α-helix proteins, hydrogen storage materials, electrode materials, nanoscale springs, etc. The electronic states of helically coiled cages of carbon material suggest that it can be a candidate for a superconductor [19]. In this regard, it is believed that HCFs can have a significant application as a structural material.

Conclusions
HCFs that came in light after the pioneering work of Motojima et al. in 1990 are designated as one of the most attractive carbon materials for electromagnetic wave absorbers, field emission, reinforcing the material in composites, supercapacitor electrodes, catalyst support, catalyst, and nanoelectronic applications. In this review article, detail of the synthesis of HCFs and effect of the experimental parameters is clearly addressed. From this review it is evident that catalyzed thermal CVD is the most suitable and widely used method for the synthesis of HCFs and related materials in terms of the product purity, high yield, and reproducibility. Mostly acetylene gas was used as carbon feedstock; and Ni, Fe, and Cu and their mixture were used as catalyst for the preparation of HCFs. The growth process, structural morphology and microstructure of the as-synthesized HCFs are affected by experimental parameters such as synthesis temperature, catalyst, composition of catalyst, particle size of catalyst, type of carbon source, flow rate of gases, atmosphere, and active shape (final shape) of the catalysts during synthesis. The anisotropy of the crystal faces of the catalyst particles are the fundamental reason for the possible coiling morphology in HCFs. Intensive research activities to improve the synthesis methods and conditions, quality, reproducibility, and high yield of HCFs reached to rewarding conclusions because of their unique three-dimensional helical structures and associated properties. Till date, there have been numerous synthesis methods described in the literature to make HCFs, however, absolute control over the helical morphology still remains a challenge.