Mononuclear Tricoordinate Copper(I) and Silver(I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin

Abstract

Reaction of two equivalents of the bulky 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with MX (being M = Cu+, Ag+; and X = Cl−, Br−, I−) in acetonitrile afforded neutral complexes of the type [MXL2] [CuClL2].2CH3CN (1a); [CuBrL2].2CH3CN (1b); [CuIL2] (1c): [AgClL2] (2a); [AgBrL2] (2b) and [AgIL2] (2c). The two aromatic groups in free ligand were found to be trans with respect to the thiourea unit, which was a reason to link the ligand molecules via intermolecular hydrogen bonding. Intramolecular hydrogen bonding was observed in all metal complexes. The copper complexes 1a and 1b are acetonitrile solvated and show not only intra- but also intermolecular hydrogen bonding between the coordinated thiourea and the solvated acetonitrile molecules. Silver complexes reported here are the first examples of structurally characterized tricoordinated thiourea-stabilized monomeric silver(I) halides. Molecular docking studies were carried out to analyze the binding modes of the metal complexes inside the active site of the human insulin (HI) protein. Analysis of the docked conformations revealed that the electrostatic and aromatic interactions of the protein N-terminal residues (i.e., Phe and His) may assist in anchoring and stabilizing the metal complexes inside the active site. According to the results of docking studies, the silver complexes exhibited the strongest inhibitory capability against the HI protein, which possesses a deactivating group, directly bonded to silver. All compounds were fully characterized by elemental analysis, NMR spectroscopy, and molecular structures of the ligand, and five out of six metal complexes were also confirmed by single-crystal X-ray diffraction.

Tuzaklamalı İyon Hareketliliği-Kütle Spektrometrisi Tekniği Kullanılarak İnsülinin Bakır ve Alkali Metal Komplekslerinin Konformasyonel Farklılıklarının Analizi

“…However, there is no change in the protein structure such as compaction as a result of the addition of atoms such as H (1.0078 Da), Na (22.9898 Da), and K (38.9637 Da), which are smaller than the copper atom. These results showed that copper metal and alkali metals interact with insulin protein in different ways in the gas phase and this difference can be monitored through conformational changes with IM-MS analysis [30][31].…”

Syntheses and structural characterization of divalent metal complexes (Co, Ni, Pd and Zn) of sterically hindered thiourea ligand and a theoretical insight of their interaction with SARS-CoV-2 enzyme

“…In silico and molecular docking studies have shown that divalent metal complexes being active antiviral agents and immunity enhancers can be very effective against SARS-CoV-2. [39] , [40] , [41] Considering the potential bioactivities of the thiourea derivatives [ 42 , 43 ], we have extended our findings to divalent metals (Co, Ni, Pd and Zn) using symmetrically substituted bulky ligand, N,N ′-bis(2,6-diethylphenyl)thiourea [44] . In addition to their syntheses, structural characterization and Hirshfeld analyses, we have applied molecular docking approach to evaluate the binding and interaction abilities of the reported compounds as a starting point for the in silico drug discovery.…”