pH-dependent coordination of metal-lisinopril complex investigated by attenuated total reflection/Fourier transform infrared spectroscopy

Abstract

In order to simulate the in vivo binding behavior of angiotensin-converting enzyme (ACE) inhibitors to the zinc-containing active center of ACE, the in vitro interaction between lisinopril and zinc or nickel ions was investigated in aqueous solutions of different pH by using attenuated total reflection (ATR)/Fourier transform infrared (FT-IR) spectroscopy with second-derivative IR spectral analysis. The results indicated that the lisinopril dissociation process occurred in a stepwise fashion during increase in pH. The IR peaks at 162 cm-1 (carbonyl stretching of tertiary amide) and at 1582 cm -1 (asymmetric COO- stretching) for lisinopril in solution at pH 3.5 shifted to 1606 and 1586 cm-1 after addition of Ni 2+ ions, respectively, but there was no marked changes in IR spectra of lisinopril after addition of Zn2+ ions. When the Zn2+ ions were added to lisinopril solution at pH 5.0, the peak at 1642 cm -1 also shifted to 1604 cm-1 and the peak at 1582 cm -1 shifted to 1586 cm-1, similar to the changes at pH 3.5 after adding Ni2+ ions. However, the peaks at 1582 and 1642 cm -1 both shifted to 1599 cm-1 after addition of Ni 2+ ions at pH 5.0 or at pH 7.3. The peak at 1576 cm-1 also shifted to 1599 cm-1 after addition of Zn2+ ions to lisinopril solution at pH 7.3. Different coordination sites or types (chelating, bridging or pseudounidentate complex) between lisinopril and Zn2+ or Ni2+ ions were proposed, based on the separation value between Vas (COO-) and Vs (COO-), and the shifting of carbonyl groups. Coordination of the secondary amine in lisinopril to metal ions was also evidenced. © 2002 Pharmaceutical Society of Japan.