A Low-barrier hydrogen bond (LBHB) is a special type of hydrogen bond. LBHBs can occur when the pKa of the two heteroatoms are closely matched, which allows the hydrogen to be more equally shared between them. This hydrogen-sharing causes the formation of especially short, strong hydrogen bonds.

Description

Standard hydrogen bonds are longer (e.g. 2.8 Å for an O···O h-bond), and the

hydrogen ion A hydrogen ion is created when a hydrogen atom loses or gains an electron. A positively charged hydrogen ion (or proton) can readily combine with other particles and therefore is only seen isolated when it is in a gaseous state or a nearly particle ...

clearly belongs to one of the

heteroatom In chemistry, a heteroatom () is, strictly, any atom that is not carbon or hydrogen. Organic chemistry In practice, the term is usually used more specifically to indicate that non-carbon atoms have replaced carbon in the backbone of the molecula ...

s. When pKa of the heteroatoms is closely matched, a LBHB becomes possible at a shorter distance (~2.55 Å). When the distance further decreases (< 2.29 Å) the bond is characterized as a single-well or short-strong hydrogen bond.

Proteins

Low barrier hydrogen bonds occur in the water-excluding environments of proteins. Multiple residues act together in a charge-relay system to control the pKa values of the residues involved. LBHBs also occur on the surfaces of proteins, but are unstable due to their proximity to bulk water, and the conflicting requirements of strong salt-bridges in protein-protein interfaces.

Enzyme catalysis

Low-barrier hydrogen bonds have been proposed to be relevant to

enzyme catalysis Enzyme catalysis is the increase in the reaction rate, rate of a process by a Biomolecule, biological molecule, an "enzyme". Most enzymes are proteins, and most such processes are chemical reactions. Within the enzyme, generally catalysis occurs ...

in two types of circumstance. Firstly, a low-barrier hydrogen bond in a charge relay network within an active site could activate a catalytic residue (e.g. between acid and base within a

catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, li ...

). Secondly, the formation of a LBHB could form during catalysis to stabilise a transition state (e.g. with substrate transition state in an oxyanion hole). Both of these mechanisms are contentious, with theoretical and experimental evidence split on whether they occur. Since the 2000s, the general consensus has been that LBHBs are not used by enzymes to aid catalysis. However, in 2012, a low-barrier hydrogen bond has been proposed to be involved in phosphate-arsenate discrimination for a phosphate transport protein. This finding might indicate the possibility of low-barrier hydrogen bonds playing a catalytic role in ion size selection for some very rare cases.

References

{{chemical bonds Chemical bonding