Hydrolysis mechanisms of BNPP mediated by facial copper(II) complexes bearing single alkyl guanidine pendants: cooperation between the metal centers and the guanidine pendants

The hydrolysis mechanisms of DNA dinucleotide analogue BNPP− (bis(p-nitrophenyl) phosphate) catalyzed by mononuclear/dinuclear facial copper(II) complexes bearing single alkyl guanidine pendants were investigated using density functional theory (DFT) calculations. Active catalyst forms have been investigated and four different reaction modes are proposed accordingly. The [Cu2(L1)2(μ-OH)]3+ (L1 is 1-(2-guanidinoethyl)-1,4,7-triazacyclononane) complex features a strong μ-hydroxo mediated antiferromagnetic coupling between the bimetallic centers and the corresponding more stable open-shell singlet state. Three different reaction modes involving two catalysts and a substrate were proposed for L1 entries and the mode 1 in which an inter-complex nucleophilic attack by a metal bound hydroxide was found to be more favorable. In the L3-involved reactions (L3 is 1-(4-guanidinobutyl)-1,4,7-triazacyclononane), the reaction mode in which an in-plane intracomplex scissoring-like nucleophilic attack by a Cu(II)-bound hydroxide was found to be more competitive. The protonated guanidine pendants in each proposed mechanism were found to play crucial roles in stabilizing the reaction structures via hydrogen bonds and in facilitating the departure of the leaving group via electrostatic attraction. The calculated results are consistent with the experimental observations that the Cu(II)–L3 complexes are hydrolytically more favorable than their L1-involved counterparts.