Theoretical and Raman spectroscopic study on the interaction of cimetidine (cim) with Mg++ and Ca++ ions.

Cimetidine (cim), a widely used drug for peptic ulcer disease, was found to affect serum levels of calcium and magnesium. The complexes of cim with Mg++ ions have been previously studied by nuclear magnetic resonance and we deepened this study by using a combined theoretical (computational analysis) and experimental (spectroscopic techniques) approach. The theoretical analysis of complexes between cim and Mg++ or Ca++ ions showed that cim is a flexible molecule, acting as a bidentate ligand toward divalent ions, using nitrogen atoms. Moreover, it suggested that Mg(Cim)2++ complex is the most stable; its structure is probably a distorted octahedron in which thè two S atoms complete the coordination shell. Raman study on the solid 2:1 cim/Mg++ and cim/Ca++ complexes supported the theoretically provided interaction sites, as suggested by the noticeable wavenumbers shift observed in vC-H and vC-N vibrations. The study was extended in the very diluted solutions (ppm) range by using the Surface Enhanced Raman Spectroscopy (SERS), mimicking the physiological active concentrations of cim. SERS spectra suggested, upon the binding of cim to silver colloids (with a mechanism that mimics the binding to a protein), the formation of a 1:1 adduct, as cim acts as a monodentate ligand. Thus, Mg++ con bridge the substrato with other bioactive structures.