The conformational stability, solvation and the assignments of the experimental infrared, Raman, 1H and 13C NMR spectra of the local anesthetic drug lidocaine

• The structure of lidocaine was optimized at the DFT B3LYP level.
• The vibrational wavenumbers and NMR chemical shifts were calculated.
• Vibrational and NMR assignments were provided by combining experimental and theoretical data.
• The Gibbs free energy changes of solvation were computed.

The structure, vibrational and 1H and 13C NMR spectra of the local anesthetic drug lidocaine were investigated by the B3LYP/6-311G∗∗ calculations. The molecule was predicted to have the non-planar cis (NCCN ∼ 0°) structures being about 2–6 kcal/mol lower in energy than the corresponding trans (NCCN ∼ 180°) forms. The calculated NCCN (9.6°) and CNCC (−132.2°) torsional angles were in a good qualitative agreement with the reported X-ray angles (3.1 and 13.0°, −102.67 and −77.9°, respectively, for H-bonded dimers). The Gibbs energy of solution of lidocaine in formamide, water, dimethylsulfoxide, acetonitrile, methanol, ethanol and chloroform solutions was estimated at the B3LYP level. The predicted affinity of lidocaine toward the alcohols, acetonitrile and chloroform solutions was in excellent agreement with the reported experimental solubility of the drug in organic solvents. The analysis of the observed vibrational spectra is consistent with the presence of lidocaine in only one conformation at room temperature. The 1H and 13C NMR spectra of lidocaine were interpreted by experimental and DFT calculated chemical shifts of the drug. The RMSD between experimental and theoretical 1H and 13C chemical shifts for lidocaine is 0.47 and 8.26 ppm, respectively.

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