Showing papers by "Pavel Hobza published in 2004"

Accurate interaction energies of hydrogen-bonded nucleic acid base pairs.

Abstract: Hydrogen-bonded nucleic acids base pairs substantially contribute to the structure and stability of nucleic acids. The study presents reference ab initio structures and interaction energies of selected base pairs with binding energies ranging from -5 to -47 kcal/mol. The molecular structures are obtained using the RI-MP2 (resolution of identity MP2) method with extended cc-pVTZ basis set of atomic orbitals. The RI-MP2 method provides results essentially identical with the standard MP2 method. The interaction energies are calculated using the Complete Basis Set (CBS) extrapolation at the RI-MP2 level. For some base pairs, Coupled-Cluster corrections with inclusion of noniterative triple contributions (CCSD(T)) are given. The calculations are compared with selected medium quality methods. The PW91 DFT functional with the 6-31G basis set matches well the RI-MP2/CBS absolute interaction energies and reproduces the relative values of base pairing energies with a maximum relative error of 2.6 kcal/mol when applied with Becke3LYP-optimized geometries. The Becke3LYP DFT functional underestimates the interaction energies by few kcal/mol with relative error of 2.2 kcal/mol. Very good performance of nonpolarizable Cornell et al. force field is confirmed and this indirectly supports the view that H-bonded base pairs are primarily stabilized by electrostatic interactions.

First local minimum of the formic acid dimer exhibits simultaneously red-shifted O?H?O and improper blue-shifted C?H?O hydrogen bonds

Abstract: The first local minimum of the formic acid dimer exhibits simultaneously red-shifted O–H⋯O and blue-shifted C–H⋯O hydrogen bonds. The improper, blue-shifted hydrogen bond was investigated by means of the NBO analysis, rehybridization model and optimization in the electric field. It was shown that the electrostatic model cannot describe the nature of the blue-shifted H-bond. From the NBO analysis it becomes evident that the formation of the O–H⋯O hydrogen bond and C–H⋯O improper hydrogen bond can be explained on the basis of an increase of electron density in the σ* antibonding O–H orbital and a decrease of electron density in the σ* antibonding C–H orbital. While the former effect is easily explained on the basis of hyperconjugation, the latter requires the existence of a new mesomeric structure characterized by delocalization of electron density from the C–H σ* antibonding orbital to the remaining part of the complex. The rehybridization model explains properly the formation of both hydrogen bonds but fails to interpret the changes of the other bonds.

Correlated ab Initio Study of Nucleic Acid Bases and Their Tautomers in the Gas Phase, in a Microhydrated Environment, and in Aqueous Solution. Part 3. Adenine

Abstract: Altogether, 14 amino and imino tautomers of adenine were studied theoretically in the gas phase, in a microhydrated environment (one and two water molecules), and in bulk water environment using the thermodynamic integration method (MD-TI), conductor-like polarizable continuum model (C-PCM, COSMO), and a hybrid model (C-PCM+ one to three explicit water molecules). The structures and relative energies of various tautomers were determined at the RI-MP2 level using the TZVPP basis set. The relative enthalpies at 0 K and relative free energies at 298 K were based on relative energies and zero-point vibration energies, temperature-dependent enthalpy terms, and entropies evaluated at the MP2/6-31G** level. The effect of bulk solvent on the relative stability of adenine tautomers was studied by molecular dynamics free energy calculations using the thermodynamic integration method and self-consistent reaction field. The dipole moment of the canonical form is rather small (2.8 D) but three rare imino tautomers have very large dipole moments (more than 10 D). The canonical form is the global minimum at all theoretical levels in the gas phase, in a microhydrated environment, and in the bulk water. Two unusual rare amino tautomers having hydrogens at N3 and N7, respectively, are less stable in the gas phase by more than 7 kcal/mol and represent the first and the second local minimum. Microhydration, as well as bulk water, stabilizes these unusual tautomers, and the energy gap between them and the canonical form is reduced, but the canonical tautomer remains the global minimum in all three phases. Relative free energies ( T ) 298 K) of these two unusual tautomers in the bulk water evaluated by molecular dynamics free energy calculations are 2.5 and 2.8 kcal/mol, which supports their coexistence in this phase. The C-PCM results agree well with the MD-TI data, and the agreement became close when considering not only the bare tautomers but their complexes with several water molecules representing first solvation shell. Other tautomers are considerably less stable (by 12 -45 kcal/mol), and neither a microhydrated environment nor bulk water can change this unfavorable tautomeric equilibrium. The theoretical data predicting the coexistence of the canonical form and the N3 and the N7 tautomers in bulk water nicely agreed with experimental data obtained from NMR measurements of the adenine tautomers in DMSO (Laxer, A.; Major, D. T.; Gottlieb, H. E.; Fischer, B. J. Org. Chem.2001, 66, 5463.)

Potential Energy Surface of the Cytosine Dimer: MP2 Complete Basis Set Limit Interaction Energies, CCSD(T) Correction Term, and Comparison with the AMBER Force Field

Abstract: The complete basis set (CBS) limit of the MP2 interaction energy and the CCSD(T) correction term determined as the difference between the CCSD(T) and MP2 interaction energies were evaluated for 17 stacked and 4 H-bonded structures of the cytosine dimer. Extrapolation to the MP2 CBS limit was done using the aug-cc-pVDZ and aug-cc-pVTZ results, and the CCSD(T) correction term was determined with the 6-31G*(0.25) basis set. Extrapolation to the CBS limit is essential in all parts of the potential energy surface and affects mainly the absolute MP2 stabilization energy. The effect on the relative stability is smaller but not negligible. The CCSD(T) correction term is for stacked structures with large overlaps of the monomers substantially repulsive but not uniform. Thus, when comparing the final estimate (abbreviated as CBS(T)) with previously used medium-level MP2/6-31G*(0.25) data, the CCSD(T) correction partially compensates for the enhanced absolute MP2 CBS stabilization but further increases the relative ...

Polar isomer of formic acid dimers formed in helium nanodroplets

Abstract: The infrared spectrum of formic acid dimers in helium nanodroplets has been observed corresponding to excitation of the “free” OH and CH stretches. The experimental results are consistent with a polar acyclic structure for the dimer. The formation of this structure in helium, as opposed to the much more stable cyclic isomer with two O–H⋯O hydrogen bonds, is attributed to the unique growth conditions that exist in helium droplets, at a temperature of 0.37 K. Theoretical calculations are also reported to aid in the interpretation of the experimental results. At long range the intermolecular interaction between the two monomers is dominated by the dipole–dipole interaction, which favors the formation of a polar dimer. By following the minimum-energy path, the calculations predict the formation of an acyclic dimer having one O–H⋯O and one C–H⋯O contact. This structure corresponds to a local minimum on the potential energy surface and differs significantly from the structure observed in the gas phase.

The mid-IR absorption spectrum of gas-phase clusters of the nucleobases guanine and cytosine

Abstract: The mid-infrared (IR) absorption spectrum of jet-cooled clusters of the nucleobases guanine and cytosine has been recorded in the 500–1800 cm−1 range by ion-dip spectroscopy. Some 30 clearly separated and sharp resonances are observed. The combination of the experimental data with new high-level ab initio calculations is consistent with a previous structural assignment and a tentative assignment is made to the K7-1E structure of guanine–cytosine. These data can serve as a test of the method in the mid-IR regime.

2 Theoretical studies of hydrogen bonding

Abstract: Theoretical procedures yielding accurate structures and stabilization energies of extended hydrogen-bonded complexes having more than 24 atoms are discussed. Accurate geometries of different types of hydrogen-bonded complexes are obtained by gradient optimization performed at correlated ab initio levels using the basis set of TZ + 2P quality. Stabilization energy of these complexes is constructed as a sum of the complete basis set limit of the MP2 stabilization energy and a correction term defined as the difference between MP2 and CCSD(T) stabilization energies. Accurate values of the latter term were obtained with medium basis sets. The results presented for the different hydrogen-bonded complexes support the fact that this correction term possesses a rather insignificant value. Comparing the geometrical and stabilization energy data with experimental results verifies the reliability of the procedure described. It can be concluded that when experimental data on extended hydrogen-bonded complexes either are missing or are not reliable, the theoretical data determined at the level described can be used with confidence.

Ferrocene-modified purines as potential electrochemical markers: synthesis, crystal structures, electrochemistry and cytostatic activity of (ferrocenylethynyl)- and (ferrocenylethyl)purines.

Abstract: Palladium-catalyzed Sonogashira cross-coupling reactions of halopurines 9-benzyl-6-chloropurine (2 a), 9-benzyl-8-bromoadenine (2 b), and 9-benzyl-2-chloroadenine (2 c) with ethynylferrocene (1) gave the corresponding (ferrocenylethynyl)purines 3 a–c in moderate to good yields. Catalytic hydrogenation of these alkynes over Pd/C afforded the respective saturated [2-(ferrocenyl)ethyl]purines 4 a–c. The crystal structures 3 a, 3 b, 4 a and 4 b as determined by X-ray diffraction show interesting solid-state interactions, markedly different for purines 3 a and 4 a on one hand and adenines 3 b and 4 b that possess a free amino group on the other. Electrochemistry of electrochemically labelled purines 3 and 4 has been studied by voltammetry and cyclic voltammetry on platinum disc electrode and the experimental oxidation potentials were confirmed and explained by ionization potentials from theoretical DFT calculations. Several compounds of this series exhibited a considerable cytostatic effect.

Theoretical calculation of the NMR spin-spin coupling constants and the NMR shifts allow distinguishability between the specific direct and the water-mediated binding of a divalent metal cation to guanine.

Abstract: The calculated intermolecular and intramolecular indirect NMR spin−spin coupling constants and NMR shifts were used for the discrimination between the inner-shell and the outer-shell binding motif of hydrated divalent cations Mg2+ or Zn2+ with a guanine base. The intermolecular coupling constants 1J(X,O6) and 1J(X,N7) (X = Mg2+, Zn2+) can be unambiguously assigned to the specific inner-shell binding motif of the hydrated cation either with oxygen O6 or with nitrogen N7 of guanine. The calculated coupling constants 1J(Mg,O6) and 1J(Zn,O6) were 6.2 and −17.5 Hz, respectively, for the inner-shell complex of cation directly interacting with oxygen O6 of guanine. For the inner-shell coordination of the cation at nitrogen N7, the calculated coupling constants 1J(Mg,N7) and 1J(Zn,N7) were 5.6 and −36.5 Hz, respectively. When the binding of the cation is water-mediated, the coupling constant is zero. To obtain reliable shifts in NMR parameters, hydrated guanine was utilized as the reference state. The calculated ...

Lipid hydration: Headgroup CH moieties are involved in water binding

Abstract: To explore the interaction potential of phospholipids, we have studied the hydration of diacyl phosphatidylcholine (PC) and methylphosphocholine (MePC), a pertinent model compound, by ir spectroscopy. Related ab initio Hartree-Fock calculations were performed for MePC. Water is considered ideal as a relevant probe molecule. Spectroscopic data for MePC reveal a strong influence of bound hydration water not only on the phosphate groups but also onto the putatively apolar CH(n) groups. The same could be demonstrated for deuterated dimyristoyl PC taken as a "complete" lipid molecule: both headgroup methyl and methylene moieties are gradually, but remarkably affected by hydration, as evidenced by strong wavenumber upshifts of C-H stretching vibration bands. These findings may originate in directed interactions of the CH(n) groups with bound water molecules, but hydration-driven conformational changes of PC headgroups could also occur. The results of the ab initio calculations rationalize the first explanation by predicting a substantial contribution of specific C-H...OH(2) interactions, mainly characterized by a dramatic loss of electron density of the sigma* antibonding molecular orbitals of C-H bonds. Hence, the propensity of the lipid headgroup methyl and methylene groups to act as donor sites in hydrogen bonding must no longer be ignored when considering the interaction potential of PCs.

The dihydrogen bond in X3C–H⋯H–M complexes (X = F, Cl, Br; M = Li, Na, K). A correlated quantum chemical ab initio and density functional theory study

Abstract: Quantum chemical calculations were performed on nine dihydrogen-bonded complexes with haloform (F3CH, Cl3CH and Br3CH) as a proton donor and alkali metal hydride (HLi, HNa and HK) as a proton acceptor. MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p) results show that the stabilization energies of these complexes are large and comparable to the stabilization energies of standard H-bonded complexes. Elongation and weakening (red shift) of the CH, HNa and HK bonds upon complexation were found while contraction and strengthening (blue shift) was observed in HLi. The H⋯H bond was found to be ionic and its ionicity is larger than that of the H⋯Y bond in standard and improper H-bonds. The calculated free energy (ΔG) revealed that only potassium hydride complexes (F3CH⋯HK, Cl3CH⋯HK and Br3CH⋯HK) are stable under standard conditions (T = 298.150 K and p = 101.325 N m−2) in the gas phase. To elucidate the role of the electrostatic contribution, the optimization of the proton donor and proton acceptor molecules in the electric field of a partner was performed. The HLi bond is contracted in the electric field of the haloform while the HM (M = Na, K) bonds are elongated and the electrostatic field itself is sufficient explanation of these phenomena. Natural bond order (NBO) and natural resonance theory (NRT) analyses were performed. The NBO analysis revealed that significant electron density was transferred from the σ bonding orbital of a proton acceptor to the antibonding σ*(CH) orbital of the proton donor. Symmetry adapted perturbation theory (SAPT) was utilized to decompose the total interaction energy into physically correct contributions.

Interactions of hydrated divalent metal cations with nucleic acid bases. How to relate the gas phase data to solution situation and binding selectivity in nucleic acids

Abstract: Binding modes of hydrated Zn2+ and Mg2+ cations to the N7 and O6 positions of guanine have been characterized by state-of-the-art ab initio model calculations. We show how differences in the electronic structure of the cationic complexes, as revealed by gas-phase computations, translate into differences in the biological function of the two studied metals. The thermodynamic driving force of the metal binding process is estimated on the basis of interaction energies and total electronic energies. The computed results unambiguously reveal that the N7 position of guanine exhibits a greater propensity to bind Zn2+ than Mg2+ while both cations have a similar affinity to bind to O6. Contrary to the intuitive expectations, however, the computed data do not suggest any superiority of the N7 inner shell binding mode for Zn2+ compared to the O6 binding. For Mg2+ the O6 inner shell binding mode is favored over the N7 one. The gas-phase data, when properly exrapolated, provide a relevant picture of many (though not all) fundamental aspects of the diversity of cation binding to nucleic acids.

Isomer selective IR experiments and correlated ab initio quantum chemical calculations support planar H-bonded structure of the 7-methyl adenine⋯adenine and stacked structure of the 9-methyl adenine⋯adenine base pairs

Abstract: In this paper we show that the stacked structures of 9-methyl adenine⋯adenine are comparably stable as the most stable hydrogen bonded structures and that the calculated IR pattern of the stacked structures is in a very good agreement with the experimental spectrum. The pair 7-methyl adenine⋯adenine on the other hand shows a nearly planar hydrogen bond arrangement and no stacked structure was observed.