Selective synthesis of mono(amidinate) chromium(II) chloride complexes and a computational insight of 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(mu-Cl)(thf)](2) (3) and [{t-BuC(NAr)(2)}Cr(mu-Cl)](2) (4) in 48 and 45% yields, respectively. X-ray analysis shows both 3 and 4 to be dimeric with the amidinate ligands eta(2)-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. (C) 2020 Elsevier Ltd. All rights reserved.