Selective synthesis of mono(amidinate) chromium(II) chloride complexes and a computational insight of their interaction with human insulin

Rare examples of mono(amidinate) CrII chloride complexes have been synthesized by applying the appropriate steric bulk and stoichiometry of the ligands. The role of the ligands and their Cr complexes as antidiabetic drugs has been studied computationally. [Display omitted] •Steric bulk is the key to selectively synthesize mono(amidinate) chromium complexes.•Sterically less bulky ligands lead to bis(amidinate) complexes.•Mono(amidinate) chromium complexes are dimeric whereas bis(amidinate) complexes are monomeric.•The molecular structures were determined by X-ray crystallography.•Computational insight was taken into account to study their interaction with human insulin. Treatment of one equivalent of sterically bulky lithiated amidinate ligands, [RC(NHAr)(NAr)] {R = Ph and Ar = 2,6-diisopropylphenyl (1); R = t-Bu and Ar = 2,6-diisopropylphenyl (2)}, with anhydrous chromium(II) chloride in tetrahydrofuran (THF) afforded, after workup in pentane or hexane, selectively rare examples of mono(amidinate) Cr(II) complexes, [{PhC(NAr)2}Cr(µ-Cl)(thf)]2 (3) and [{t-BuC(NAr)2}Cr(µ-Cl)]2 (4) in 48 and 45% yields, respectively. X-ray analysis shows both 3 and 4 to be dimeric with the amidinate ligands η2-coordinated to one Cr atom each and the Cl ligands bridge the two Cr centers. Owing to the low steric bulk of the amidinate ligand in 3, one thf ligand is coordinated to each Cr atom. A sterically less bulky ligand, [RC(NHAr)(NAr)] {R = t-Bu and Ar = 2,6-dimethylphenyl (5)} instead led to a bis(amidinate) Cr(II) complex (6). A molecular docking simulation of the ligands and metal ligated complexes was performed with the human insulin protein (PDB code: 3Q6E.) to gauge the potential of the metal complexes as effective drug candidates for the treatment of type I and type II diabetes. Docking simulations of the ligands and metal complexes showed a strong binding inside the active site cleft. The docked poses showed important binding features, mostly because of the interactions due to the aromatic moieties of the amidinate ligands.