Hydrogen-stretching vibrational circular dichroism spectroscopy: absolute configuration and solution conformation of selected pharmaceutical molecules.
The vibrational circular dichroism (VCD) spectra of several chiral antiarrhythmic drugs (quinidine, flecainide, RAC 109, and propranolol) and chiral anti-inflammatory drugs (ibuprofen and naproxen) in the OH-, NH- and CH-stretching regions are reported. The absolute configurations of some of these drugs are identified by comparison to VCD spectra of similar molecules and by VCD intensity calculations on fragments of the drugs, utilizing either the locally distributed origin gauge (LDO) model or a priori vibronic coupling theory (VCT) methods. The most abundant conformations of propranolol, flecainide and RAC 109 in non-aqueous solution are also identified from the VCD spectra. This study demonstrates the utility of VCD in this spectral region for identification of solution conformation and absolute configuration for pharmaceuticals of moderate size. The conformations deduced from the VCD spectra provide insight into the stereospecific binding of the antiarrhythmic drugs.
Freedman
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TB
Department of Chemistry, Syracuse University, NY 13244-4100, USA. tbfreedm@syr.edu
Long
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Citra
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Nafie
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LA
D000889:Anti-Arrhythmia Agents / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002942:Circular Dichroism; D005424:Flecainide / Q000737:chemistry; D006859:Hydrogen; D007052:Ibuprofen / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry; D009288:Naproxen / Q000737:chemistry; D011433:Propranolol / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry; D011802:Quinidine / Q000737:chemistry; D014732:Vibration
D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009281:Naphthalenes; D011760:Pyrrolidinones; C061605:RAC 109; D009288:Naproxen; D006859:Hydrogen; D011433:Propranolol; D011802:Quinidine; D005424:Flecainide; D007052:Ibuprofen