Raman and SERS study on cimetidine–metal complexes with biomedical interest

Abstract

Cimetidine (cim) is one of the most potent histamine H 2 -receptor antagonists for inhibiting excessive acid secretion caused by histamine; it has been hypothesized that the therapeutic effects can be related to its interactions with metal ions. Raman spectra of the solid cim with Co(II), Cu(II), Ni(II) and Zn(II) metal complexes show that they can adopt two different structures: one is octahedral and the other, with Zn(II), is probably tetrahedral. The octahedral structure appears to be distorted both by the different metal ions as well as by the different anion present. The study was extended to very dilute solutions (ppm range) by using the surface-enhanced Raman scattering (SERS) technique, mimicking the physiological concentrations of cim and its metal complexes. SERS spectra suggest that, upon the binding of cim to silver colloids, the formation of stable 1 : 2 cim-metal complexes is excluded, the formation of 1 : 1 adduct appearing more probable; in this product the metal reaches its total coordination shell by complexion with water molecules. To better explain the binding mechanism of cim to a metal (Ag) surface, we performed theoretical B3LYP calculations on cim alone as well as on cim bonded to an Ag 2 metal cluster in presence of water, observing a sufficiently good agreement between experimental and theoretical wavenumbers.

Spectroscopic Studies and DFT Calculations of Cimetidine Complexes with Transition Metal Ions

“…shows three bands at 9324, 14431 and 24964 cm -1 assigned to the 3 Table 1.Selected stretching vibrations (cm -1 ) for cimetidine and complexes 1-9.…”

“…Cimetidine, (scheme 1), 2-cyano-1-methyl-3-(2-[(5-methyl-1H-imidazol-4-yl)-methyl-thio]-ethyl)-guanidine, is a potent histamine H 2 -receptor antagonist, which inhibits excessive acid secretion caused by histamine, and is used for treatment of peptic ulcer [1]. This drug has the ability to chelate metal ions in blood plasma and in different tissues [2], and it had previously been suggested that the main therapeutic action of cimetidine might be mediated by its interactions with essential metal ions [3]. It resulted interesting to find out whether cimetidine could compete for Cu II ion against biological ligands such as albumin [1].…”

“…The copper ions are six-coordinated, by two imidazole nitrogens and two thioeter sulfur atoms from two different cimetidine molecules; the coordination sphere is completed by two cyano nitrogens from neighbouring molecules. Soto et al [7] and Bianucci [8] synthesised and characterised by IR and UV-vis absorption spectroscopies, coordination compounds of the type [M(cime) 2 ]X 2 (M = Co 2+ , Ni 2+ , X = NO 3 -, BF 4 - [7] and ClO 4 - [8]). Vibrational spectra (IR and Raman) of cimetidine and their complexes [M(cime) 2 ](ClO 4 ) 2 , where M corresponds to Cu II , Cd II , Co II and Ni II , were obtained and calculated using semiempirical methods: MNDO, AM1 and PM3 [9].…”

Recent advances in linear and nonlinear Raman spectroscopy. Part VI

“…Bonora and co‐workers used SERS to analyze the structures of Cimetidine (cim), one of the most potent histamine H2‐receptor antagonists for inhibiting excessive acid secretion caused by histamine, complexed with various metal ions, Co(II), Cu(II), Ni(II), and Zn(II), to understand the differences in therapeutic effects for these metals . The art conservation field has seized upon the opportunity opened up by the power of SERS to enable the identification of microscopic amounts of organic molecules used as artists' colorants in complex matrixes, such as biomaterials.…”

Cimetidine : A Review

“…This drug has the ability to chelate metal ion in blood plasma and in different tissue 12 . and it had previously been suggested that the main therapeutic action of cimetidine might be mediated by its interaction with essential metal ions. 13,14 …”