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 is of prime importance for understanding the role of zinc(II)-based cofactors in 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 in 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 environments of the nitrite anions in these complexes are nearly identical, despite the dissimilarity in the Lewis-acidity of the [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 the [(Me₂PzQu)₂Zn^II]²⁺ core is the most efficient in promoting nitrite–thiol interactions due to the ease of available hemilabile coordination sites at the Lewis acidic [Zn^II]. Detailed UV-vis studies in tandem with computational investigation, for the first time, provide an unambiguous demonstration of the nitrous acid (HNO₂) intermediate generated through an intramolecular proton-transfer from thiol to nitrite at zinc(II).