Infrared vibrational spectra as a structural probe of gaseous ions formed by caffeine and theophylline

Abstract

Ionic hydrogen bond (IHB) interactions, resulting from the association of ammonia and the two protonated methylxanthine derivatives, caffeine and theophylline, have been characterized using infrared multiphoton dissociation (IRMPD) spectroscopy and electronic structure calculations at the MP2/aug-cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. The proton-bound dimer (PBD) of caffeine and ammonia exhibits a low binding energy and was found to be elusive under the experimental conditions due, most probably, to collision-induced dissociation of the complex with helium buffer gas before IRMPD irradiation. The IRMPD spectrum of a PBD of theophylline and ammonia was obtained and revealed bidentate IHB formation within the complex, which greatly increased the binding energy relative to the most stable isomer of the PBD of caffeine and ammonia. The IRMPD spectra of the protonated forms of caffeine and theophylline have also been obtained. The spectrum of protonated caffeine showed dominant protonation at the N(9) site, whereas the spectrum of protonated theophylline showed a mixture of two isomers. The first protonated isomer of theophylline exhibits protonation at the N(9) site and the second isomer demonstrated protonation at the C(6) carbonyl oxygen. The protonated carbonyl isomer of theophylline cannot be produced as a result of direct protonation and is thus suggested to be a consequence of proton-transport catalysis (PTC) initiated by the electrostatic interaction between water and N(9) protonated theophylline. Calculated anharmonic spectra have been simulated at the B3LYP/6-311+G(d,p) level of theory. It is shown that calculated anharmonic frequencies significantly outperform calculated harmonic frequencies in providing simulated IRMPD spectra in all cases.

Experimental and Theoretical Investigation of the Proton-Bound Dimer of Lysine

“…The MAD between all calculated bond lengths at the B3LYP/6-31+ G(d) and MP2/6-31+G(d,p) levels of theory is found to be only 0.019Å, or 1.4 % of the average molecular bond length. These observations would suggest that B3LYP/6-31+G(d) performs similarly as the MP2/6-31+G(d) and MP2/6-31+ (d,p) levels of theory for the purpose of obtaining optimized geometries of (Lys) 2 H + , which is also consistent with what is found for optimizations done at higher levels of theory on similar sized systems that we have described recently [37,38]. This comparison is very useful since optimizations and notably, frequencies calculated using the MP2 method are considerably more costly than those obtained with B3LYP coupled with equivalent sized basis sets.…”

“…B3LYP is a relatively reliable and economical computational method and is extensively employed in the investigation of biological molecules [32][33][34][35][36][37][38].…”

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

“…Recently, we have been exploring functionality of methylxanthines such as caffeine and theophylline by probing the structures of electrosprayed gaseous ions using the powerful technique of infrared multiple photon dissociation (IRMPD) spectroscopy, coupled with electronic structure calculations [4]. Structures of both protonated caffeine and theophylline, as well as the proton-bound dimer (PBD) of ammonia and theophylline have been determined accurately and unambiguously using this technique.…”

Consecutive Fragmentation Mechanisms of Protonated Ferulic Acid Probed by Infrared Multiple Photon Dissociation Spectroscopy and Electronic Structure Calculations

“…IRMPD, in combination with electronic structure calculations, is a powerful technique for structural elucidation studies such as this . IRMPD spectroscopy experiments were performed at the Centre de Laser Infrarouge d'Orsay (CLIO) and have been described in detail previously [8,12,13,24,31]. The IR-FEL beam was directed into a Bruker (Bruker; 40 Manning Road, Billerica, MA, USA 01821) Esquire 3000+ ion-trap mass spectrometer, equipped with an electrospray ionization interface.…”

“…Relative Gibbs free energies (298 K) are reported in kJ mol −1 Electronic structure calculations have been performed using the Gaussian 09 software package [32]. All geometry optimizations and associated frequency calculations have been performed at the B3LYP/6-311+G(d,p) level of theory, which has been shown to be a reliable protocol, with a good compromise between accuracy and cost, for smaller systems such as those described here [13,14,16,24,[33][34][35][36]. All harmonic frequencies obtained at this level of theory were scaled by 0.9679 [37] in order to compensate for errors arising from the use of a harmonic oscillator approximation in calculating the frequencies, as well as long range electron correlation effects.…”