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

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 bct wen 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) spcctroscopy 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 1642cm(-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 1586cm(-1) after addition of Ni2+ 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 1586cm(-1), similar to the changes at pH 3.5 after adding Ni2+ ions. However, the peaks at 1582 and 1642cm(-1) both shifted to 1599cm(-1) after addition of Ni2+ 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 pseudo-unidentate complex) between lisinopril and Zn2+ or Ni2+ ions were proposed. based on the separation value between V-as (COO-) and V-s (COO-), and the shifting of carbonyl groups. Coordination of the secondary amine in lisinopril to metal ions was also evidenced.