Estimation of gas-phase acidities of deoxyribonucleosides: An experimental and theoretical study

Abstract

We determined the gas-phase acidities (⌬H acid ) of four deoxyribonucleosides, i.e., 2=-deoxyadenosine (dA), 2=-deoxyguanosine (dG), 2=-deoxycytidine (dC), and 2=-deoxythymidine (dT) by applying the extended kinetic method. The negatively charged proton-bound hetero-dimeric anions, [A Ϫ H Ϫ B]Ϫ of the deoxyribonucleosides (A) and reference compounds (B) were generated under electrospray ionization conditions. Collision-induced dissociation spectra ofϪ were recorded at four different collision energies using a triple quadrupole mass spectrometer. The abundance ratios of the individual monomeric product ions were used to determine the ⌬H acid of the deoxyribonucleosides. The obtained ⌬H acid value follows the order dA Ͼ dC Ͼ dT Ͼ dG. The ⌬G acid (298 K) values were determined by using ⌬G acid ϭ ⌬H acid -T⌬S acid where the ⌬H acid and ⌬S acid values were determined directly from the kinetic method plots. The ⌬H acid values were also predicted for the deoxyribonucleosides at the B3LYP/6-311ϩG**//B3LYP/6-311G** level of theory. The acidity trend obtained from the computational investigation shows good agreement with that obtained experimentally by the extended kinetic method. Theoretical calculations provided the most preferred deprotonation site as C5=-OH from sugar moiety in case of dA, and as ϪNH 2 (dC and dG) or ϪNH- . The determination of thermochemical properties of these molecules in the gas phase could be of importance for biological reasons because biological environment can be relatively nonpolar in nature. Moreover, the gasphase studies explore the reactivity of molecules and ions without solvent effects. To date, mass spectral studies have been focused towards analysis and structural characterization of deoxyribonucleosides [2][3][4][5][6][7][8][9][10]. While thermochemical properties of individual nucleobases have been well studied experimentally in the gas phase, the studies on nucleosides are limited [11][12][13][14][15][16].Xia et al.[11] performed extensive calculations on proton affinities (PAs) of nucleosides by the density functional approach. The PA of the four deoxyribonucleosides, i.e., 2=-deoxyadenosine (dA), 2=-deoxyguanosine (dG), 2=-deoxycytidine (dC), and 2=-deoxythymidine (dT) were reported to be in the order of dG Ͼ dC Ͼ dA Ͼ dT, and this order is similar to the PA order of the free bases (G Ͼ C Ͼ A Ͼ T). They concluded the protonation features of deoxyribonucleosides were less changed compared with the corresponding free bases. Donna et al. [12] determined the PA of dA and demonstrated the effective use of the kinetic method for the thermochemical measurement of multifunctional molecules like nucleosides and nucleobases. Besides the wide array of proton affinity studies on deoxyribonucleosides [13][14][15][16], there have been no experimental or theoretical reports on the gas-phase acidities (⌬H acid ) of deoxyribonucleosides. In this study, we report the first determination of ⌬H acid of dA, dG, dC, and dT through application of the extended kinetic method. We have also calculated the ...

Different Conformations of 2′-Deoxycytidine in the Gas and Solid Phases: Competition between Intra- and Intermolecular Hydrogen Bonds

“…The difference was interpreted through an orbital stabilizing effect resulting from the intramolecular O5'-H13 … O2 hydrogen bond in syn conformers. The MP2 value of deprotonation enthalpy of dC of 1411.7 kJ/mol is in very good agreement with the experimental value of 1409±2.5 kJ/mol 20.…”

Gas-phase structure and reactivity of the keto tautomer of the deoxyguanosine radical cation

“…35,36 Thus in the gas phase, ionisation of dG enhances its acidity by B415 kJ mol À1 , somewhat less than what we found for 9MG (B470 kJ mol À1 ), but still a significant enhancement of acidity. Indeed, the enhanced acidity of dG + is close to the PA of dC (988.4 kJ mol À1 ) 38 and this suggests that proton transfer within the ionised base pair may become viable. As noted in the introduction, a mechanism proposed for strand breaking in ionised DNA involves hydrogen-atom abstraction from the sugar moiety induced by deprotonation of the guanine radical cations.…”

Mass Spectrometry in India

“…The present 14 C dates of the samples pushes back the antiquity of custard apple on Indian soil to the second millennium BC, favoring a group of specialists proposing diverse arguments for Asian-American trans-oceanic contacts before the discovery of America by Columbus in 1492 AD. 427,428 Chemical extraction methods were developed to remove the interference of the stable isobar 53 Cr in the measurements of concentrations of 53 Mn in rocks that might help to understand Earth surface processes that occurred in time periods not accessible with other cosmogenic nuclides. 429 Similarly, the interference of 146 Nd in the measurement of 146 Sm, a long-lived radionuclide produced during the formation of supernovae, has also been taken care of and this study was aimed at obtaining information on nuclear synthesis at the time of the formation of our solar system.…”

“…51 The gas-phase acidities of many dicarboxylic acids and four deoxyribonuclosides were determined by the kinetic method. 52,53 Collaboration between Vairamani with Parthasarathy of the National Geophysical Research Institute (NGRI), Hyderabad, a constituent laboratory of CSIR, resulted in the discovery of fullerenes in low-grade metamorphosed Proterozoic shungite from Karelia, Russia and in the Cretaceous-Tertiary boundary layer at Anjar, Kutch, India, representing a significant contribution towards understanding the formation of fullerenes in nature. 54,55 In collaboration with Chattopadhyaya at the Centre for Cellular and Molecular biology (CCMB), Hyderabad (another constituent laboratory of CSIR), interactions of membrane sterols, cholesterol and 7-DHC (an immediate biosynthetic precursor of cholesterol) with neuronal receptor (serotonin 1A receptor) were studied under pathogenic conditions, such as the Smith-Lemli-Opitz syndrome (SLOS) associated with defective cholesterol biosynthesis.…”