Role of Ancillary Ligands in S-nitrosothiol and NO Generation from Nitrite-Thiol Interactions at Mononuclear Zinc(II) Sites

Abstract

Generation of S-nitrosothiol (RSNO) and nitric oxide (NO) mediated by zinc(II) coordination motifs are of prime importance for understanding the role of zinc(II)-based cofactors in various redox-signalling pathways. This study uniquely employs a set of mononuclear [L₂Zn^II]²⁺ cores (where L = Me₄PzPz/Me₂PzPy/Me₂PzQu) for introducing subtle alterations of the primary coordination sphere and investigates the role of ligand tuning on the transformation of NO₂^– in the presence of thiols. Single crystal X-ray diffraction (SCXRD) analyses on [L₂Zn^II–X](X) (where X = perchlorate/triflate) illustrate consistent changes in the bond distances, thereby showing variations of the metal–ligand interactions depending on the nature of the heterocyclic donor arms (pyrazole/pyridine/quinoline). Moreover, such tuning of the ligands affects the Lewis-acidity of the [L₂Zn^II]²⁺ cores as evaluated by ³¹P NMR and SCXRD studies on the 1:1 acid-base adducts [L₂Zn^II(OPEt₃)]²⁺. Crystallographic and ¹⁵N NMR spectroscopic analyses on the nitrite complexes [L₂Zn^II(κ²-nitrite)](ClO₄) reveal that the chemical environment of the nitrite anions in these complexes are nearly identical, despite the dissimilarity in the Lewis-acidity of [L₂Zn^II]²⁺ cores. Interestingly, RSNO and NO generation from the reactions of [L₂Zn^II(κ²-nitrite)](ClO₄) with 4-tert-butylbenzylthiol (^tBuBnSH) exhibits that [(Me₂PzQu)₂Zn]²⁺ core is the most efficient in promoting nitrite-thiol interactionsdue to the ease of available hemilabile coordination site at the Lewis acidic [Zn^II]. Detailed UV-vis studies in tandem with computational investigation, for the first time, provide an unambiguous demonstration of nitrous acid (HNO₂) intermediate generated through an intramolecular proton-transfer from thiol to nitrite at zinc(II).