The generation of an oxygen-insensitiveandinexpensive H2 production electrocatalyst is essential in the pursuitof a H2-based renewable energy infrastructure. The cobaloxime complexes containing axial pyridinesare considered as one of thebest candidates for thisrole due totheir active H2production catalysisin aerated aqueous solution. However, the practical applications of these cobaloximeshave been stalled due to their slowcatalyticrate and narrow active chemical space (active only near neutral conditions).We have probed the catalytic reactivity of the cobaloxime core in details to realize that the primarily coordinated hydrogen-bonded oxime moietyplays the crucial role to tune the H2evolutionreactivity. Intriguingly, this oxime-based proton relaycollapses under acidic conditions (pH < 5) to limitthe H2production by cobaloximes only atneutral condition (pH ~7) in water. Inspired by the metalloenzymearchitecture, we have integratedvariable combinations of peripheral protic groups (such as secondary amine, carboxylic acid, and phenolic-OH)around the identicalcobaloxime corethatareappended through theaxial pyridine ligand. The strategic incorporation of these protic groups surrounding the cobalt centresignificantly improves(~2.0-9.5 times) their electrocatalytic H2productionratewhile expanding the active chemical space for H2production even into the acidic aqueous conditions (pH 3-7). The three dimensional crystallographic data along with the detailed one-and two-dimensional NMR studies have revealed the formation of an intricate hydrogen-bonding network between the peripheral basic functionalities and specifically positioned water and chloride molecules. This hydrogen bonding nexus generated a water mediated auxiliary proton relayaround the cobaloxime skeleton to stimulate the catalytic H2production activity. These results highlight that the catalytic activity of the artificial catalysts can be fine-tuned by the proper incorporation of enzyme-inspired, outer coordination sphere features around a synthetic catalyst framework