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 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 1642 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 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 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 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 pseudounidentate 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.
Wang
Shun-Li
SL
Department of Medical Research & Education, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Chuang
Chi-Hsiang
CH
Lin
Shan-Yang
SY
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017706:Lisinopril / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D015032:Zinc / Q000737:chemistry*
D000806:Angiotensin-Converting Enzyme Inhibitors; D012996:Solutions; D009532:Nickel; D017706:Lisinopril; D015032:Zinc