Peptide Hydrolysis by Metal-Cyclen Complexes and Their Analogues: Insights from Theoretical Studies

In the present DFT study, mechanisms of peptide hydrolysis by Co(III)- and Cu(II)-containing complexes of 1,4,7,10-tetraazacyclododecane (cyclen), 1-Co and 1-Cu, respectively, and 1-oxa-4,7,10-triazacyclododecane (oxacyclen), 2-Co and 2-Cu, respectively, and their analogues have been investigated. In addition, the effects of the ligand environment, pendant (an organic group containing a recognition site) and metal ion (Co(III), Cu(II), Ni(II), Zn(II), Cd(II), and Pd(II)), on the energetics of this reaction have been elucidated. The reactant of the 1-Co complex exists in the syn–anti conformation, while that of 1-Cu in the syn–syn form. For both these complexes, stepwise and concerted mechanisms were found to occur with similar barriers. The substitution of one of the nitrogen atoms in the cyclen macrocycle to create oxacyclen should occur at position 10 in the Co(III) case and at position 4 in the Cu(II) case. A comparison between the barriers using the common conformation (syn–anti) of 1-Co and 2-Co show...

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