Spectrochimica Acta Part A 65 (2006) 191–195 Solid and solution NMR studies of the complexation of Ag + with the trans isomer of captopril: Biological activities of this high blood pressure drug along with its Ag + complex Anvarhusein A. Isab ∗ , Mohamed I.M. Wazeer Contribution from Department of Chemistry, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia Received 5 June 2005; received in revised form 14 October 2005; accepted 14 October 2005 Abstract Complexation of Ag + with captopril, 1-[(2S)-3-mercapto-2-methylpropionyl]-l-proline, has been studied by 1 H and 13 C-NMR spectroscopy. The equilibrium constants for the trans to cis isomers of captopril bound to Ag + were measured by 1 H NMR spectroscopy. It is observed that the trans isomer of the drug binds more strongly to Ag + between pH 5 and 8, as shown by the broadening of the trans isomer’s resonances in 13 C NMR spectra on complexation. A monodentate complexation of the trans captopril with Ag + via the thiol site is proposed based on the solid-state NMR and IR data. A superior antimicrobial activity is exhibited by the Cap–Ag(I) complex compared to captopril ligand itself against Heterotrotropic Plate Counts (HPC), Pseudomonas aeruginosa and Fecal streptococcus bacteria. © 2005 Elsevier B.V. All rights reserved. Keywords: Captopril; Ag(I)–captopril complex; CP MAS of Ag(I)–captopril; Antimicrobial Activity 1. Introduction Captopril, 1-[(2S)-3-mercapto-2-methylpropionyl]-l-pro- line, is an orally active drug for the treatment of high blood pressure [1–3]. High blood pressure can result from the production of angiotensin II from inactive angiotensin I, the conversion being catalyzed by angiotensin-converting enzyme [4,5], which is a zinc containing metallo-enzyme [6]. The clinical trials have shown that side effects are sometimes associated with this drug [7,8] especially in patients receiving high doses (∼450 mg/d). These side effects include a dry cough, skin rashes, dysgeusia, and neutropenia often associated with zinc and/or copper depletion [9–11]. Hughes et al. [12] have studied the complexation of captopril with Zn(II), Cd(II) and Pb(II) by potentiometric titrations. The log  values of captopril:Zn 2+ ratio of 1:1, 2:1 and 3:1 is found to be 5.38, 11.66 and 15.30, respectively, indicating a stronger complexation at a higher captopril to Zn 2+ ratio. It is well known that proline-containing peptides normally exist as an equilibrium mixture of cis and trans isomers with ∗ Corresponding author. Tel.: +966 3 8602645; fax: +966 3 8604277. E-mail addresses: aisab@kfupm.edu.sa (A.A. Isab), miwazeer@kfupm.edu.sa (M.I.M. Wazeer). respect to the peptide bond involving the proline amino group [13–15]. Thus, captopril is expected to be present in aqueous solution as trans and cis forms, with the relative population of the two forms dependent on the protonation state of the molecule [16–18]. Hassall et al. [19] have assumed that conformationally restricted angiotensin converting enzyme inhibitors require a trans amide bond of captopril when binding to enzyme. In view of the above restriction, it is of interest to study the metal-ion binding to captopril, since 1 H and 13 C NMR spectroscopy offers a powerful tool to distinguish between the isomers [17]. In the present paper, we report the pH * titration of captopril with Ag + by 1 H and 13 C NMR in solution, in an effort to iden- tify which isomer is binding preferentially to Ag + . Solid-state 13 C spectra of the ligand and the complex were also recorded, to identify the nature of the complex in the absence of compli- cations of cis/trans equilibria [17]. 2. Experimental 2.1. Chemicals The captopril was a gift from the Bristol–Myers Squibb Insti- tute for Medical Research, Princeton, NJ. The 99.7% D 2 O, 36% 1386-1425/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.saa.2005.10.030