Raman spectra of cimetidine Zn++ and Cu++ metallo-complexes with biomedical interest.

Cimetidine (Cim) is currently used for treating peptic ulcers since it acts as an inhibitor of excessive acid secretion caused by histamine. It has been hypothesized that the therapeutic effect as well as some of its side effects are mediated by the interaction with essential metal ions. This hypothesis is supported from the following evidences: copper, in presence of Cim, enhances its anti-inflammatory and anti-ulcer properties; the involvement of Cim in rheumatoid arthritis evolution could be related to the well-established role of copper against this disease; male sexual dysfunctions frequently reported during treatment with Cim could derive from its interaction with zinc, whose important role in sexual activity is well documented. Cu(Cim)2(ClO4)2 and Zn(Cim)2(ClO4)2 were prepared by adding to a hot Cim solution a water solution of Cu(ClO4).6H2O or Zn(ClO4)2.6H2O, causing thus the precipitation of the insoluble metallo-complexes. Spectra evidence noticeable changes as a consequence of complexation, suggesting that the structure of the two metallo-complexes is quite different. In particular, in the metallo-complexes, the VC=N band is blue-shifted compared to the corresponding vibration in pure Cim, in which the 2176 cm-1 peak suggests that the nitrile group is involved in strong hydrogen bonds; therefore we suppose that Cim structure changes as a consequence of complexation. Moreover, the observation of two VON bands in the Zn-complex suggests that two Cim molecules bind the central metal ion with two different metal-CN bond lengths. The existence of different structures is confirmed by Raman spectra. In fact, a different behavior is observed in the VC=N spectral region near 1600 cm-1, in the VC-N region at -1280 cm-1 and in the VG-S region at -700 cm-1. Both the VC=N and VC-N vibrations are attributed to the imidazole ring, whose spatial orientation depends on the conformation of the sulphur containing side chain. Because Cim acts as a bidentate ligand through Nimidazole and Sether atoms, it is evident that the modality of the attack to Cu++ and Zn++ is quite different. Moreover, the Raman spectrum of Cu(II)-Cim complex shows a band at ~ 210 cm-1, which is not present in Zn(II)-Cim salt. We tentatively attribute this peak to the vCu-Cu stretching vibration on the basis of literature data on complexes containing metal-metal bonds, whose wavenumbers are located in the 150-230 cm-1 range. This finding suggests that, in thè Cu++ complex, Cim behaves as a bridging bidentate ligand able to bind two Cu(II) atoms, leading thus to a dimeric structure of the type [Cu2Cim4(H20)2] (C1O4)4.