LaPlanche, Laurine A.
M.S. (Master of Science)
Department of Chemistry
Solution (Chemistry); Chemistry; Physical organic; Lidocaine
The conformations of lidocaine, C₆H₃(CH₃)₂NHCOCH₂N(CH₂CH₃)₂, a local anesthetic, were determined in solution using nuclear magnetic resonance (NMR) lanthanide-induced shifts (LIS) and conformational energy calculations. The LIS were obtained from a plot of observed induced shifts vs. molar ratios of lanthanide shift reagent (LSR) to lidocaine, Lₒ/Sₒ. The method of successive dilution was employed at constant substrate concentration, Sₒ. The LSR used were La, Pr, Nd, Sm, Eu, Ho, Er, Tm and Yb(fod)₃ reagents; all are paramagnetic except La. Corrections for the complex formation shifts were made using La(fod)₃. Separation of contact and pseudo-contact contributions to the observed LIS was performed and the resulting pseudocontact shift was used in the McConnell-Robertson equation. Further calculations were performed by fitting the observed LIS to the total two-term pseudo-contact equation. Conformational energy and LIS calculations were done by setting the molecule initially at the crystal structure subrotation angle values and allowing the molecule to rotate about these angles. Two predominant conformations, referred to as the trans and cis configurations, may be deduced for lidocaine using conformational energy calculation and the two-term equation for pseudo-contact shifts. Both forms are probably present in solution. The angle between the plane of the ring and the plane of the amide group (NHCO) was found to be 90°. Cis and trans refer to angles of 60 or 170 + 20° for the dihedral angle N-C-C-N. The results show the preferred conformation of the Ln(fod)₃ lidocaine complexes is the trans configuration for Ln = Pr, Nd, Sm, Eu, Ho, Er and Tm and the cis configuration for the Yb(fod)₃ lidocaine complex.
Jasmani, Halila, "The use of lanthanide induced shifts and conformational energy calculations in the determination of the conformations of lidocaine in solution" (1983). Graduate Research Theses & Dissertations. 6378.
xv, 150 pages
Northern Illinois University
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