The sodium cation-bound dimer of theophylline: IRMPD spectroscopy of a highly symmetric electrostatically bound species

Sodium cation-carbonyl interactions resulting from the formation of a sodium cation-bound dimer (SCBD) of a common bronchodilator, theophylline have been probed using infrared multiple photon dissociation (IRMPD) spectroscopy and electronic structure calculations. Energies have been determined at the MP2(full)/aug-cc-pCVTZ//B3LYP/6-311+G(d,p) level of protocol for all heteroatoms involved in sodium interactions, including sodium and at the MP2(full)/6-311+G(2d,2p)//B3LYP/6-311+G(d,p) level of protocol for all remaining heavy and hydrogen atoms. Six stable isomers of the SCBD of theophylline have been proposed within a range of relative Gibbs free energies of ∼36 kJ mol−1 (298 K). The most favourable isomer (10.9 kJ mol−1 over the next isomer at 298 K) exhibits an average zero net dipole moment due to free rotation of theophylline molecules about a CO⋯Na+⋯OC axis, facilitated by the relatively large interatomic distance (4.28 Å) between the carbonyl oxygen atoms. This is also shown to effectively isolate the theophylline molecules from interaction resulting in a significant reduction in the observed vibrational anharmonicity. Such a feature provides a chemical system that can be more suitably simulated by a spectrum calculated using a harmonic, rather than anharmonic oscillator approximation. This is important since the system described here is 37 times more costly to produce using an anharmonic oscillator approximation relative to the analogous harmonic calculation at the B3LYP/6-311+G(d,p) level of protocol with the same computational resources. Accurate characterization of both the free and sodiated carbonyl stretches, as well as several other frequencies of the SCBD of theophylline gives insight into cation–molecule interactions and also provides a useful contribution to the growing database of gas phase infrared spectral assignments.

Infrared multiphoton dissociation spectroscopy and electronic structure calculations have been used to characterize the structure of a symmetric and electrostatically bound sodiated dimer of theophylline.Figure optionsDownload high-quality image (63 K)Download as PowerPoint slide