Nitrile hydratases (NHases) are non-heme Fe-III or non-corrin Co-III containing metalloenzymes that possess an N2S3 ligand environment with nitrogen donors derived from amidates and sulfur donors derived from cysteinates. A closely related enzyme is thiocyanate hydrolase (SCNase), which possesses a nearly identical active-site coordination environment as CoNHase. These enzymes are redox inactive and perform hydrolytic reactions; SCNase hydrolyzes thiocyanate anions while NHaso converts nitriles into amides. Herein an active CoNHase metallopeptide mimic, [Co(III)NHase-m1] (NHase-m1 = AcNH-CCDLP-CGVYD-PA-COOH), that contains Co-III in a similar N2S3 coordination environment as CoNHase is reported. [Col'INHase-ml] was characterized by electrospray ionization-mass spectrometry (ESI-MB), gel-permeation chromatography (GPO), Co K-edge X-ray absorption spectroscopy (Co S: 2.21 A; Co-N: 1.93 A), vibrational, and optical spectroscopies. We find that [Co(III)NHase-m1] will perform the catalytic conversion of acrylonitrile into acrylamide with up to 58 turnovers observed after 18 h at 2500 (pH 8.0). FTIR data used in concert with calculated vibrational data (mPWPW91/aug-cc-TZVPP) demonstrates that the active form of [Co(III)NHase-m1] has a ligated SO2 (v = 1091 cm(-1)) moiety and a ligated protonated SO(H) (v = 928 cm-1) moiety; when only one oxygenated cysteinate ligand (i.e., a mono-SO2 coordination motif) or the bis-SO2 coordination motif are found within [CollINHase-ml] no catalytic activity is observed. Calculations of the thermodynamics of ligand exchange (B3LYP/aug-cc-TZVPP) suggest that the reason for this is that the SO2/SO(H) equatorial ligand motif promotes both water dissociation from the Coln-center and nitrile coordination to the Co"-center. In contrast, the underor overoxidized motifs will either strongly favor a five coordinate Coln-center or strongly favor water binding to the Coln-center over nitrile binding.