 This binding forms a 5-members chelate ring that looks similar to the binding of hydroxamic acid.The amide bond of the carbamoyl phosphonate provide a hydrogen bond donor for protein interactions and the amide group has an electron donating ability that provides strong Zn2+ chelation.The carbamoyl phosphonate zinc binding groups have a net negative charge that hinders cell penetration of these inhibitors and restricts them to the extracellular space.This cell penetration prevention contributes to the low toxicity of these inhibitors.