Conformational characteristics decisive for their biological action of organotin metallotherapeutics using a combination of NMR methods and in silico calculations

1. Zoupanou^a, Christina N. Banti ^b, Sotiris K. Hadjikakou ^b, M.E Stathopoulou^b, S. Kiriakidi^a, Carlos Silva Lopez ^c, Uroš Javornik^d , Sotiris K. Hadjikakou ^a ,T.Mavromoustakos^a

^aDepartment of Chemistry, National and Kapodistrian University of Greece Zografou, 15771, Athens, Greece

^bSection of Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45110 Ioannina, Greece

^cDepartment of Organic Chemistry, University of Vigo, Lagoas-Marcosende Campus, Vigo, Spain

^dSlovenian NMR Centre, National Institute of Chemistry of Ljubljana, Hajdrihova 19, Slovenia

DOI:  10.62579/JAGC0013

Abstract

This study involves the structure elucidation and conformational analysis of three synthetic metallotherapeutics organotin (IV) derivatives of cholic acid (CAH) with the formulate R₃Sn(CA) (R= Ph- (1), n-Bu- (2)) and R₂Sn(CA)₂ (R= Me- (3). The structures of compounds (1–3) were assigned using a combination of homonuclear and heteronuclear 2D NMR experiments. Subsequently, ¹¹⁹Sn NMR experiments and semi-empirical quantum mechanic computations (method PM6) were applied to determine the geometry surrounding the tin atom. Results showed that their optimized geometry is distorted tetrahedral and thus their biological activity of these compounds may be related with the conformation of atoms which endue the metal of Sn. In silico molecular docking studies were performed to the   ER-α (estrogen receptor alpha ligand) justifying the compounds’ biological activity.

Key Words :  metallotherapeutics, organotin, NMR spectroscopy, semi-empirical quantum mechanic computations

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