Electronic transitions of guanine tautomers, their stacked dimers, trimers and sodium complexes

Planar and nonplanar geometries of the keto-N9H and keto-N7H tautomers of the guanine base of DNA as well as the hydrogen bonded complexes of these species with three water molecules each were optimized using the density functional theory at the B3LYP/6-31G** level. Geometries of the isolated bases were also optimized using the ab initio approach at the MP2/6-31G** level. The isolated keto-N9H and keto-N7H tautomers as well as their hydrogen bonded complexes with three water molecules each were solvated in bulk water employing the polarized continuum model (PCM) of the self-consistent reaction field theory (SCRF). Stacked dimers and trimers of both the tautomers of guanine were generated by placing the planar forms of the species at a fixed distance of 3.5 A from the neighboring one and rotating one molecule with respect to the other by 110 degrees for the keto-N9H form and 90 degrees for the keto-N7H form which corresponded to total energy minima at the B3LYP/6-31G** level. Geometry optimization for the cation of the monomer of guanine was performed at the same level of theory, and its solvation in bulk water was treated using the PCM model of the SCRF theory. The geometries of complexes of the two tautomers of guanine with a Na+ ion each were optimized at the B3LYP/6-31G** level, and the Na+ ion is predicted to bind with the keto-N9H tautomer preferentially. While the complex of the keto-N7H form of guanine with three water molecules in gas phase is slightly more stable than the corresponding complex of the keto-N9H form of guanine, the reverse is true in bulk water. Stacking interactions enhance the relative stability of the keto-N9H tautomer over that of the keto-N7H tautomer, suggesting that in bulk solutions, the former would be dominant. Electronic spectra of the isolated tautomers of guanine, those of their complexes with three water molecules each, the (keto-n9h and keto-n7h) cation of guanine, the complexes of the tautomers with a Na+ ion each, the stacked dimers and trimers of the two tautomers were calculated using configuration interaction involving single electron excitations (CIS). The relative absorption intensities of the two tautomers of guanine near 275 and 248 nm in the monomer, dimer, and trimer are predicated to be in the opposite order. Thus the absorption intensity oscillation observed using a guanine aqueous solution can be explained in terms of oscillation of relative populations of the two tautomers of the molecule. The 248 nm absorption peak would be appreciably red-shifted on formation of the cation of guanine. Binding of the Na+ ion with the two tautomers of guanine reduces intensities of their transitions appreciably and also it causes large red-shifts in the same.     

The effect of configuration of gas phase protonated ethenedicarboxylates on their low energy collision induced dissociation behaviour

Low energy collision induced dissociation (CID) spectra were measured by a triple stage quadrupole mass spectrometer for the [MH]⁺ ions of diethyl and dimethyl esters of maleic, fumaric, citraconic and mesaconic acids. A very high degree of stereospecificity was observed for the geometrically isomeric diethyl esters. The cis esters give rise to very abundant [MH? EtOH]⁺ and [MH? EtOH? C₂H₄]⁺ ions, while the trans isomers exhibit very abundant [MH? C₂H₄]⁺ and [MH? 2 C₂H₄]⁺ ions. The highly stereospecific processes indicate that the double bond configuration is retained in the protonated species under the conditions of the experiment.     

Low-energy tautomers and conformers of neutral and protonated arginine.

The relative stabilities of zwitterionic and canonical forms of neutral arginine and of its protonated derivative were studied by using ab initio electronic structure methods. Trial structures were first identified at the PM3 level of theory with use of a genetic algorithm to systematically vary geometrical parameters. Further geometry optimizations of these structures were performed at the MP2 and B3LYP levels of theory with basis sets of the 6-31++G** quality. The final energies were determined at the CCSD/6-31++G** level and corrected for thermal effects determined at the B3LYP level. Two new nonzwitterionic structures of the neutral were identified, and one of them is the lowest energy structure found so far. The five lowest energy structures of neutral arginine are all nonzwitterionic in nature and are clustered within a narrow energy range of 2.3 kcal/mol. The lowest energy zwitterion structure is less stable than the lowest nonzwitterion structure by 4.0 kcal/mol. For no level of theory is a zwitterion structure suggested to be the global minimum. The calculated proton affinity of 256.3 kcal/mol and gas-phase basicity of 247.8 kcal/mol of arginine are in reasonable agreement with the measured values of 251.2 and 240.6 kcal/mol, respectively. The calculated vibrational characteristics of the low-energy structures of neutral arginine provide an alternative interpretation of the IR-CRLAS spectrum (Chapo et al. J. Am. Chem. Soc. 1998, 120, 12956-12957).     

The bimolecular hydrogen-deuterium exchange behavior of protonated alkyl dipeptides in the gas phase

As part of an ongoing characterization of the intrinsic chemical properties of peptides, thermal hydrogen-deuterium exchange has been studied for a series of fast-atom-bombardment-generated protonated alkyldipeptides and related model compounds in the reaction with D₂O, CH₃OD, and ND₃ in a Fourier transform ion cyclotron resonance mass spectrometer. Despite the very large basicity difference between the dipeptides and the D₂O and CH₃OD exchange reagents, efficient exchange of all active hydrogen atoms occurs. From the kinetic data it appears that exchange of the amino, amide, and hydroxyl hydrogens proceeds with different efficiencies, which implies that the proton in thermal protonated dipeptides is immobile. The selectivity of the exchange at the different basic sites is governed by the nature of both the dipeptide and the exchange reagent. The results indicate that reversible proton transfer in the reaction complexes, which effectuates the deuterium incorporation, is assisted by formation of multiple hydrogen bonds between the reagents. Exchange is considered to proceed via the intermediacy of different competing intermediate complexes, each of which specifically leads to deuterium incorporation at different basic sites. The relative stabilization of the competing intermediate complexes can be related to the relative efficiencies of deuterium incorporation at different basic sites in the dipeptide. For all protonated dipeptides studied, the exchange in the reaction with ND₃ proceeds with unit efficiency, whereas all active hydrogen atoms are exchanged equally efficiently. Evidently specific multiple hydrogen bond formations are far less important in the reversible proton transfers with the relatively basic ammonia, which allows effective randomization of all active hydrogen atoms in the reaction complexes.     

Mid-IR spectra of different conformers of phenylalanine in the gas phase

The experimental mid- and far-IR spectra of six conformers of phenylalanine in the gas phase are presented. The experimental spectra are compared to spectra calculated at the B3LYP and at the MP2 level. The differences between B3LYP and MP2 IR spectra are found to be small. The agreement between experiment and theory is generally found to be very good, however strong discrepancies exist when -NH2 out-of-plane vibrations are involved. The relative energies of the minima as well as of some transition states connecting the minima are explored at the CCSD(T) level. Most transition states are found to be less than 2000 cm(-1) above the lowest energy structure. A simple model to describe the observed conformer abundances based on quasi-equilibria near the barriers is presented and it appears to describe the experimental observation reasonably well. In addition, the vibrations of one of the conformers are investigated using the correlation-corrected vibrational self-consistent field method.     

Systematic theoretical investigations on the tautomers of thymine in gas phase and solution

The tautomers of thymine are systematically calculated using various methods. The order of the relative stability, dipole moment as well as solvent effect of the 13 isomers are investigated. The one-step transition process by proton transfer in gas phase and in solution (H₂O or CH₃OH), which acts as both proton donor and acceptor, are exhaustively studied, meanwhile, the internal rotation between two related isomers in the gas phase is also investigated. Furthermore, the energy barrier of each transition is calculated and the results show that both H₂O and CH₃OH could reduce the energy barrier. Comparisons between the activation energies of all the producing processes of each tautomer as well as temperature effect on the producing processes are made. The calculation results also indicated that the diketo is the most stable isomer both in gas phase and in solution, additionally, it is thermodynamically as well as dynamically favored.     

Proton and sodium ion affinities of glycine and its sodium salt in the gas phase. Ab initio calculations

The energies of protonation and Na⁺ cationization of glycine (GLY) and its (GLY ? H + Na) salt in the gas phase were calculated using ab inltio calculations. The proton affinity of GLY, valued at the MP2/6–31G*//3-21G level, is 937 kJ mol^?1. The amino function is confirmed to be the most favourable site of protonation: ‘proton affinities’ of the carbonyl and hydroxyl functions are calculated to be 75 and 180 kJ mol^?1, respectively, lower than that of NH₂ at the MP2/6-31G*//3–21G level. Calculations performed up to the MP2/6–31G*//3–21G level give the Na⁺ affinity of GLY as 189 kJ mol^?1 and the H⁺ and Na⁺ affinities of (GLY – H + Na) as 1079 and 298 kJ mol^?1, respectively. The geometries of all neutral and protonated species optimized with the 3–21G basis set are described. Both H* and Na⁺ cations complex preferably between the nitrogen atom and the carbonyl oxygen atom, leading to pseudo-five-membered ring structures in which Na? O and Na? N bonds lengths are greater than 2 Å.     

Gas phase ion chemistry of methyl acetate,methyl propanoate and their enolic tautomers. An experimental approach

From a combination of isotopic substitution, time-resolved measurements and sequential collision experiments, it was proposed that whereas ionized methyl acetate prior to fragmentation rearranges largely into \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm CH}_3 \mathop {\rm C}\limits^ + ({\rm OH}){\rm O}\mathop {\rm C}\limits^{\rm .} {\rm H}_2 $\end{document}, in contrast, methyl propanoate molecular ions isomerize into \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop {\rm C}\limits^. {\rm H}_2 {\rm CH}_2 \mathop {\rm C}\limits^ + ({\rm OH}){\rm OCH}_3 $\end{document}. Metastably fragmenting methyl acetate molecular ions are known predominantly to form H₂?OH together with \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm CH}_3 - \mathop {\rm C}\limits^ + = {\rm O} $\end{document}, whereas ionized methyl propanoate largely yields H₃CO˙ together with \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm CH}_3 {\rm CH}_2 - \mathop {\rm C}\limits^ + = {\rm O} $\end{document}. The observations were explained in terms of the participation of different distonic molecular ions. The enol form of ionized methyl acetate generates substantially more H₃CO˙ in admixture with H₂?OH than the keto tautomer. This is ascribed to the rearrangement of the enol ion to the keto form being partially rate determining, which results in a wider range of internal energies among metastably fragmenting enol ions. Extensive ab initio calculations at a high level of theory would be required to establish detailed reaction mechanisms.     

A TDDFT study of the optical response of DNA bases, base pairs, and their tautomers in the gas phase

We present calculations of the optical response of the DNA bases and base pairs both in their normal and tautomeric forms in the gas phase, using time-dependent density functional theory (TDDFT). These calculations are performed in real time within the adiabatic approximation with a basis of local orbitals. Our results for the individual bases are in good agreement with experiment and computationally more demanding calculations of chemical accuracy. The optical response of base pairs indicates that the differences between normal and tautomeric forms in certain cases are significant enough to provide a means of identification.     

Multidimensional separations of ubiquitin conformers in the gas phase: Relating ion cross sections to H/D exchange measurements

Investigating gas-phase structures of protein ions can lead to an improved understanding of intramolecular forces that play an important role in protein folding. Both hydrogen/deuterium (H/D) exchange and ion mobility spectrometry provide insight into the structures and stabilities of different gas-phase conformers, but how best to relate the results from these two methods has been hotly debated. Here, high-field asymmetric waveform ion mobility spectrometry (FAIMS) is combined with Fourier-transform ion cyclotron resonance mass spectrometry (FT/ICR MS) and is used to directly relate ubiquitin ion cross sections and H/D exchange extents. Multiple conformers can be identified using both methods. For the 9+ charge state of ubiquitin, two conformers (or unresolved populations of conformers) that have cross sections differing by 10% are resolved by FAIMS, but only one conformer is apparent using H/D exchange at short times. For the 12+ charge state, two conformers (or conformer populations) have cross sections differing by <1%, yet H/D exchange of these conformers differ significantly (6 versus 25 exchanges). These and other results show that ubiquitin ion collisional cross sections and H/D exchange distributions are not strongly correlated and that factors other than surface accessibility appear to play a significant role in determining rates and extents of H/D exchange. Conformers that are not resolved by one method could be resolved by the other, indicating that these two methods are highly complementary and that more conformations can be resolved with this combination of methods than by either method alone.     

Ab initio studies of aspartic acid conformers in gas phase and in solution

Systematic and extensive conformational searches of aspartic acid in gas phase and in solution have been performed. For the gaseous aspartic acid, a total of 1296 trial canonical structures and 216 trial zwitterionic structures were generated by allowing for all combinations of internal single-bond rotamers. All the trial structures were optimized at the B3LYP/6-311G* level and then subjected to further optimization at the B3LYP/6-311++G** level. A total of 139 canonical conformers were found, but no stable zwitterionic structure was found. The rotational constants, dipole moments, zero-point vibrational energies, harmonic frequencies, and vertical ionization energies of the canonical conformers were determined. Single-point energies were also calculated at the MP2/6-311++G** and CCSD/6-311++G** levels. The equilibrium distributions of the gaseous conformers at various temperatures were calculated. The proton affinity and gas phase basicity were calculated and the results are in excellent agreement with the experiments. The conformations in the solution were studied with different solvation models. The 216 trial zwitterionic structures were first optimized at the B3LYP/6-311G* level using the Onsager self-consistent reaction field model (SCRF) and then optimized at the B3LYP/6-311++G** level using the conductorlike polarized continuum model (CPCM) SCRF theory. A total of 22 zwitterions conformers were found. The gaseous canonical conformers were combined with the CPCM model and optimized at the B3LYP/6-311++G** level. The solvated zwitterionic and canonical structures were further examined by the discrete/SCRF model with one and two water molecules. The incremental solvation of the canonical and zwitterionic structures with up to six water molecules in gas phase was systematically examined. The studies show that combining aspartic acid with at least six water molecules in the gas phase or two water molecules and a SCRF solution model is required to provide qualitatively correct results in the solution.     

A theoretical investigation of the low energy conformers of the isomers glycine and methylcarbamic acid and their role in the interstellar medium

We have theoretically investigated the low energy conformers of neutral glycine (NH(2)CH(2)COOH) and its isomer methylcarbamic acid (CH(3)NHCOOH) in the gas phase. A total of 16 different levels of the theory, including CCSD(T), MP2 and B3LYP methods with various Pople and Dunning type basis sets with and without polarization and diffuse functions were used. We found eight low energy glycine conformers, where the heavy atoms in three have a planar backbone, and four low energy methylcarbamic acid conformers all with non-planar backbones. Interestingly at all levels of theory, we found that the most stable methylcarbamic acid conformer is significantly lower in energy than the lowest energy glycine conformer. The MP2 level and single point CCSD(T) calculations show the lowest energy methylcarbamic acid conformer to be between 31 to 37 kJ mol(-1) lower in energy than the lowest energy glycine conformer. These calculations suggest that methylcarbamic acid might serve as a precursor to glycine formation in the Interstellar Medium (ISM). We also report the theoretical harmonic vibrational frequencies, infrared intensities, moment of inertia, rotational constants and dipole moments for all of the conformers. In order to understand how glycine or methylcarbamic acid might be formed in the ISM, larger calculations which model glycine or its isomer interacting with several surrounding molecules, such as water, are needed. We demonstrate that B3LYP method should provide a reliable and computationally practical approach to modeling these larger systems.     

Unusual platinum complexes in the gas phase

Previously unknown cationic platinum complexes Pt(C₅H₄N)(C₅H₅N)⁺ and Pt(C₅H₄N)⁺, where platinum atom forms an unusual three-membered metallacycle with a deprotonated pyridine molecule, were detected in the gas phase by mass spectrometry and structurally characterized by DFT quantum-chemical calculations.     

Palladium acetate complexes in the gas phase

New palladium acetate complexes, Pd₂(OOCMe) ₄ ⁺ , Pd₂(OOCMe) ₃ ⁺ , Pd₂(OOCMe) ₂ ⁺ , and Pd₂(OOCMe)⁺ were detected in the thermal decomposition products of trans-Pd(Py)₂(OOCMe)₂ by mass spectrometry with direct ion source. The geometric and electronic structures of the Pd₂(μ-OOCMe) ₄ ⁺ cation and the Pd₂(OOCMe)₄ molecule were established by quantum chemical calculations (DFT with the PBE1PBE hybrid exchange correlation potential in the 6-31G*/SDD basis set) and natural orbital analysis.     

Mass spectrometric identification of ring-chain tautomers of 4-cyano-3-pyrazolidones in the gas phase

Analysis of the electron impact mass spectra of a series of 4-cyano-3-pyrazolidones, which manifest ring-chain tautomerism in polar solvents, showed that these compounds also exist in the gas phase as a mixture of tautomers, which undergo characteristic fragmentation. The quantitative tautomer ratio in this series is a function of electronic and steric substituent effects. The fragmentation pathways for each of the tautomers were determined using high-resolution mass spectrometry.M. V. Lomonosov Moscow State University, 119899 Moscow. Yerevan State University, 375025 Yerevan. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp 1525–1530, November, 1995 Original article submitted November 1, 1995.     

Aggregates of cucurbituril complexes in the gas phase

The self-organization of cucurbit[n]uril (n = 7 and 8, CBs) complexes was probed by electrospray mass spectrometry. The self-association of CB complexes is a general phenomenon but shows some dependence on the absence, presence, and type of included guest molecules.     

Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase,in a microhydrated environment and in aqueous solution. guanine: surprising stabilization of rare tautomers in aqueous solution

Altogether eight keto and enol tautomers of guanine were studied theoretically in the gas phase, in a microhydrated environment (1 and 2 water molecules) and in bulk water. The structures of isolated, as well as mono- and dihydrated tautomers were determined by means of the RI-MP2 method using the extended TZVPP (5s3p2d1f/3s2p1d) basis set. The relative energies of isolated tautomers included the correction to higher correlation energy terms evaluated at the CCSD(T)/aug-cc-pVDZ level. The relative enthalpies at 0 K and relative free energies at 298 K were based on the above-mentioned relative energies and zero-point vibration energies, temperature-dependent enthalpy terms and entropies evaluated at the MP2/6-31G level. The keto form having hydrogen atom at N7 is the global minimum while the canonical form having hydrogen atom at N9 represents the first local minimum at all theoretical levels in vacuo and in the presence of 1 and 2 water molecules. All three unusual rare tautomers having hydrogens at N3 and N7, at N3 and N9, and also at N9 and N7 are systematically considerably less stable and can be hardly detected in the gas phase. The theoretical predictions fully agree with existing theoretical as well as experimental results. The effect of bulk solvent on the relative stability of guanine tautomers was studied by self-consistent reaction field and molecular dynamics free energy calculations using the thermodynamic integration method. Bulk solvent, surprisingly, strongly favored these three rare tautomers over all remaining low-energy tautomers and probably only these forms can exist in water phase. The global minimum (tautomer with hydrogens at N3 and N7) is by 13 kcal/mol more stable than the canonical form (3rd local minimum). Addition of one or two water molecules does not change the relative stability order of isolated guanine tautomers but the respective trend clearly supports the surprising stabilization of three rare forms.     

Structural motifs of DNA complexes in the gas phase

DNA duplexes are known to be quite stable in the condensed phase but recent mass spectrometry results have shown that DNA complexes are also stable (at least for a limited time) in the gas phase. However, very little is known about the overall shape of the complexes in a solvent-free environment and what factors influence that shape. In this article, we present recent ion mobility and molecular modeling results that address some issues concerning the gas-phase conformations of DNA duplexes. Examples include the effect of metal ions on Watson–Crick base pairing, investigating the onset of helicity in duplexes as a function of strand length, comparison of the stability of C·G and A·T base pairs, and examining the formation of quadruplex structures.     

Nature of minor-groove binders-DNA complexes in the gas phase

The structure of noncovalent complexes of DNA duplex with minor groove binders (mG-binders) has been analyzed by state of the art molecular dynamics (MD) simulations. More than 3.3 micros of MD trajectories (including 4 x 0.5 micros trajectories) were collected for the Dickerson's dodecamer bound to DAPI, Hoechst 33258, and Netropsin. Comparison of these trajectories with control simulations in water allowed us to determine that the extreme dehydration and partial neutralization occurring during electrospray experiments does not produce the disruption of the DNA:mG-binder complexes or the dissociation of the two strands of the duplex. Irrespective of the drug and the simulation conditions the mG-binders remains bound to the DNA near the preferential binding position in aqueous conditions. Large distortions appear in the two DNA strands, which maintain however a memory of the original DNA duplex structure in water, and a general helical-like conformation.