Ab initio vibrational calculations on ara-T molecule: application to analysis of IR and Raman spectra

The FTIR and FT-Raman spectra are reported for the arabinonucleoside ara-T (1-beta-D-arabinofuranosylthymine), which shows antiviral activity. The accurate knowledge of the vibrational modes is a prerequisite for the elucidation of drug-nucleotide and drug-enzyme interactions. The FTIR and FT-Raman spectra of ara-T were recorded from 4000 to 30 cm(-1). A tetradeuterated derivative (deuteration at N3, and hydroxyl groups O'2, O'3, and O'5) was synthesized and the observed isotopic shifts in its spectra were used for the vibrational analysis of ara-T. The theoretical frequencies and the potential energy distribution (PED) of the vibrational modes of ara-T were calculated using the ab initio Hartree-Fock/3-21G method. An assignment of the vibrational spectra of ara-T is proposed considering the scaled PED and the observed band shifts under deuteration. The scaled ab initio frequencies were in reasonable agreement with the experimental data.     

Ab initio Models for Six-Center Multiple Proton Exchange and Ion Pair Formation Assisted by Lewis Acids

High level ab initio and density functional calculations, extrapolated to QCISD(T)/6-311+G(3df,2p)//MP2/6-31+G^**+ZPE, reveal that cyclic ion pairs can form in the hydrogen bonded complexes of haloboric acids BH_nX_3-n–HX, X=F, Cl, with Lewis bases HX, H₂O, CH₃OH, and NH₃, even in isolation (e.g., in the gas phase). The intrinsic acidities (deprotonation energies) required for protonation of these bases with formation of gas phase ion pairs are calculated to be <295 kcal/mol for water, <301 kcal/mol for methanol, and <306 kcal/mol for ammonia; such values are common for acidic sites in zeolites. All gas phase ion pairs prefer symmetric bidentate or tridentate structures. In the other cases where hydrogen bonded complexes prevail, symmetric ion pair-like transition structures for multiple hydrogen exchange are computed.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s0089400060563     

Introducing a novel method based on the imperialistic competitive algorithm to determine fluorine intermolecular potential from ab initio calculations and calculation of some properties via MD simulations

In this work, the possibility of obtaining an accurate site-site potential model suitable for use in molecular dynamics (MD) simulations of fluorine from ab initio calculations has been explored. The exploration was made on ab initio calculations. To reduce the ab initio pair potentials into a site-site potential, a higher significance was assigned to the configuration which is more stable. For this purpose, the imperialistic competitive algorithm (ICA) was implemented as a powerful optimisation tool. The calculated second virial coefficients were compared to the experimental values to test the quality of the presented intermolecular potential. The relative error for the calculated second virial coefficient ranged from 0.1 to 5.6%. MD simulations were used to evaluate the ability of the proposed intermolecular potential function. The relative error for the MD simulations ranged from 0.5 to 5.2%. The results are in good agreement with experimental data.     

A Comparative Semiempirical, Ab initio and DFT Study of Decarbonylation of Cyclic Ketones Part 1: Thermal Fragmentation of Cyclopropanone

Calculations using different quantum mechanical methods including semiempirical (MNDO,AM1 and PM3), ab initio (RHF and MP2 calculations using the 6-311G and 6-311++G^** basis sets), and density functional theory (LSDA, BP, MIXBP and B3LYP, i.e., B3LYP/6-311+G**//B3LYP/6-31G*) have been performed on the thermal fragmentation of cyclopropanone to ethylene and carbon monoxide. All RHF calculations predict a concerted single step mechanism for this conversion. The estimated activation energies vary from 34.4 to 54.6 kcal·mol^-1, mainly localized around 37±2 kcal·mol^-1, depending on the method. Whereas the calculated RHF reaction energies also varied from 14.5 to -33.3 kcal·mol^-1, the B3LYP/6-311+G**//B3LYP/6-31G* method predicts the experimental value (-17.7 kcal·mol^-1) within experimental uncertainties. Remarkably, semiempirical AM1 and PM3 methods and simple DFT calculations, LSDA, predict comparable results to the more advanced methods. UHF ab initio calculations predict the same single step mechanism, whereas a multistep biradical mechanism with an unrealistically low activation energy is favored by the semiempirical methods. Structures of the activated complex of the single step mechanism, estimated by different methods, are very similar and consistent with a nonlinear cheletropic [_2s + _2a] reaction, as predicted by the orbital symmetry rules and earlier EHT calculations.Electronic Supplementary Material available.     

Ab initio molecular orbital studies of closed shell flavins

Ab initio calculations with a (7 s 3 p) basis set are performed on uracil, lumazine, alloxazine and various isoalloxazines. The results as total energies and charge distributions are discussed in relation to the biochemical behaviour of the flavins. The calculations correctly predict equilibrium situations in the alloxazine-isoalloxazine system and explain the high affinity for nucleophilic addition at N₅ in the flavins. The reduction of flavins and their reoxidation by oxygen are discussed.     

Ab initio simulations of Cu binding sites on the N-terminal region of prion protein

The human prion protein binds Cu²⁺ ions in the octarepeat domain of the N-terminal tail up to full occupancy at pH 7.4. Recent experiments have shown that the HGGG octarepeat subdomain is responsible for holding the metal bound in a square-planar configuration. By using first principle ab initio molecular dynamics simulations of the Car–Parrinello type, the coordination of copper to the binding sites of the prion protein octarepeat region is investigated. Simulations are carried out for a number of structured binding sites. Results for the complexes Cu(HGGGW)(wat), Cu(HGGG), and [Cu(HGGG)]₂ are presented. While the presence of a Trp residue and a water molecule does not seem to affect the nature of the copper coordination, high stability of the bond between copper and the amide nitrogen of deprotonated Gly residues is confirmed in all cases. For the more interesting [Cu(HGGG)]₂ complex, a dynamically entangled arrangement of the two domains with exchange of amide nitrogen bonds between the two copper centers emerges, which is consistent with the short Cu–Cu distance observed in experiments at full copper occupancy.     

Ab initio molecular dynamics study of the hydration of the formohydroxamate anion

We apply ab initio molecular dynamics (AIMD) to study the hydration structures and electronic properties of the formohydroxamate anion in liquid water. We consider the cis- nitrogen-deprotonated, cis- oxygen-deprotonated, and trans- oxygen-deprotonated formohydroxamate tautomers. They form an average of 6.3, 6.9, and 6.0 hydrogen bonds with water molecules, respectively. The predicted pair correlation functions and time dependence of the hydration numbers suggest that water is highly structured around the nominally negatively charged oxime oxygen in O-deprotonated tautomers but significantly less so around the nitrogen atom in the N-deprotonated species. Wannier function analysis suggests that, in the O-deprotonated anions, the negative charge is concentrated on the oxime oxygen, while in the N-deprotonated case, it is partially delocalized between the nitrogen and the adjoining oxime oxygen atom.     

Lanthanide complex coordination polyhedron geometry prediction accuracies of ab initio effective core potential calculations

The ability to efficiently and accurately predict solid-state geometries of lanthanide coordination compounds efficiently and accurately is central for the design of new ligands capable of forming stable and highly luminescent complexes. Accordingly, we present in this paper a report on the capability of various ab initio effective core potential calculations in reproducing the coordination polyhedron geometries of lanthanide complexes. Starting with all combinations of HF, B3LYP and MP2(Full) with STO-3G, 3-21G, 6-31G, 6-31G* and 6-31+G basis sets for [Eu(H₂O)₉]³⁺ and closing with more manageable calculations for the larger complexes, we computed the fully predicted ab initio geometries for a total of 80 calculations on 52 complexes of Sm(III), Eu(III), Gd(III), Tb(III), Dy(III), Ho(III), Er(III) and Tm(III), the largest containing 164 atoms. Our results indicate that RHF/STO-3G/ECP appears to be the most efficient model chemistry in terms of coordination polyhedron crystallographic geometry predictions from isolated lanthanide complex ion calculations. Moreover, both augmenting the basis set and/or including electron correlation generally enlarged the deviations and aggravated the quality of the predicted coordination polyhedron crystallographic geometry. Our results further indicate that Cosentino et al.’s suggestion of using RHF/3-21G/ECP geometries appears to be indeed a more robust, but not necessarily, more accurate recommendation to be adopted for the general lanthanide complex case. Figure Graphical visualization of unsigned mean errors, UME(Eu-L)s, involving only the interatomic distances between the europium central ion and the oxygen atoms of the coordination polyhedron of the cation nona-aqua-europium(III) for various model chemistries, all compared to the “Cambridge Structural Database 2004” crystallographic geometry     

G2, G3, and complete basis set calculations on the thermodynamic properties of triazane

As a follow-up study to our study on tetrazane (N₄H₆), we present computed thermodynamic properties of triazane (N₃H₅). Calculated properties include optimized geometries, infrared vibrations, enthalpy of formation, enthalpy of combustion, and proton affinities. We have also mapped the potential energy surface as the molecule is rotated about the N-N bond. We have predicted a specific enthalpy of combustion for triazane of about -20 kJ g⁻¹. Figure Schematic diagram of the dielectric barrier discharge (left) and typical temporal profiles of voltage and current, as obtained from the simulations (right)     

Ab initio predictions of structural and elastic properties of struvite: contribution to urinary stone research

In the present work, we carried out density functional calculations of struvite – the main component of the so-called infectious urinary stones – to study its structural and elastic properties. Using a local density approximation and a generalised gradient approximation, we calculated the equilibrium structural parameters and elastic constants C _ijkl . At present, there is no experimental data for these elastic constants C _ijkl for comparison. Besides the elastic constants, we also present the calculated macroscopic mechanical parameters, namely the bulk modulus (K), the shear modulus (G) and Young's modulus (E). The values of these moduli are found to be in good agreement with available experimental data. Our results imply that the mechanical stability of struvite is limited by the shear modulus, G. The study also explores the energy-band structure to understand the obtained values of the elastic constants.     

Ab initio and dielectric studies of succinic acid and maleic acid in 1,4-dioxane

In a continuing effort to understand the hydrogen bond through the study of dielectric and computational conformal studies of dilute solutions, succinic acid and maleic acid are studied in solutions of 1,4-dioxane solvent. Dielectric studies give an account of the net dipole moment of the system under study, which is then compared with the values obtained from conformal analysis. The dielectric measurements were made at 303 K at a frequency of 9.83 GHz using a X-band microwave test bench in order to determine the relaxation times and the dipole moments. The static dielectric permittivity and the high frequency dielectric permittivity were measured using a LCR meter and an Abbe's refractometer, respectively. The results are inspected in comparison with the dipole moment results of ab initio calculations of some of the conformers in gas phase and in liquid phase. Gaussian-03 software package with 6–31G(d) basis set optimisation was used for this purpose. Onsager's reaction field model is used to study the solvation of the dicarboxylic acids in 1,4-dioxane. The results are interpreted in terms of the intermolecular and intramolecular hydrogen bond interactions in the dilute systems.     

Ab initio protein modelling reveals novel human MIT domains

Database searches can fail to detect all truly homologous sequences, particularly when dealing with short, highly sequence diverse protein families. Here, using microtubule interacting and transport (MIT) domains as an example, we have applied an approach of profile-profile matching followed by ab initio structure modelling to the detection of true homologues in the borderline significant zone of database searches. Novel MIT domains were confidently identified in USP54, containing an apparently inactive ubiquitin carboxyl-terminal hydrolase domain, a katanin-like ATPase KATNAL1, and an uncharacterized protein containing a VPS9 domain. As a proof of principle, we have confirmed the novel MIT annotation for USP54 by in vitro profiling of binding to CHMP proteins.

Structured summary

USP8 binds:CHMPs 1A 1B 2A 2B 4CUSP54 binds:CHMPs 1B 2A 2B 4C 6     

Ab initio conformational maps for disaccharides in gas phase and aqueous solution

Ab initio conformational maps for beta-lactose in both the gas phase and in aqueous solution have been constructed at the HF/6-31G(d,p) level of calculation. The results of the gas-phase ab initio calculations allow us to conclude that a rigid conformational map is able to predict the regions of the minima in the potential energy surface of beta-lactose, in full agreement with those found in the relaxed conformational map. The solvation effects do not give rise to any new local minimum in the potential energy surface of beta-lactose, but just change the relative Boltzmann populations of the conformers found in the gas-phase calculations. The values obtained for heteronuclear spin coupling constant (3J(H,C)), using the seven most stable conformers in solution are in good agreement with the available experimental values. This is a good indication that ab initio rigid conformational maps can be reliably used to sort the most stable conformers of beta-lactose.     

G2, G3, and complete basis set calculations of the thermodynamic properties of cis- and trans-triazene

Following our recent study on triazane, we present a follow-up study on the thermodynamic properties of triazane’s unsaturated analog, triazene. We predict optimized structural parameters, vibrational frequencies, enthalpies of formation, enthalpies of combustion, specific enthalpies of combustion, and proton affinities. Our results indicate that the cis form of triazene has a specific enthalpy of combustion of −15.2 kJ g⁻¹ and the trans form has a specific enthalpy of combustion of −14.7 kJ g⁻¹. Figure Structures of cis- and trans-triazane, N₃H₃     

3-Silaoxetane and 3-silathietane: structure and reactivity studies on the basis of spectroscopic data and theoretical calculations

The ab initio and DFT calculations (structural parameters, electron localization function (ELF)) on 3-silaoxetane 3,3-dimethyl-2,2,4,4-tetraphenyl-1-oxa-3-silacyclobutane (1) and 3-silathietane 3,3-dimethyl-2,2,4,4-tetraphenyl-1-sila-3-thiacyclobutane (2) show the cyclobutane ring in 2 as being non-planar with a C-Si-C angle of 89.2° and a C-S-C angle of 93.3°, whereas the cyclobutane ring in 1 is planar with an unusual small bond angle at the silicon atom of 74.7°, which can only be explained by bent bonds. Since the synthesis was performed in water, small bent angles cannot be indicative for high reactivity. The Raman spectra of 1 and 2 were then recorded and analyzed in the 1800-200 cm⁻¹ spectral region at various temperatures (300-10 K) with the help of the DFT calculation results (harmonic vibrational wavenumbers, Raman scattering activities). Although the wavenumber shifts are quite small, the subtle changes in the spectral features of the 3-silaoxetane and phenyl rings vibrational modes may indicate a loss of symmetry in 1 (between 200 and 150 K) and a possible phase transition in 2 (at about 200 K). Furthermore, the Raman spectra of 1 and 2 confirmed the ELF calculation results, excluding any bond interaction between the silicon and the oxygen or sulfur atom.     

Ab initio computational study of beta-cellobiose conformers using B3LYP/6-311++G**

The molecular structure of 27 conformers of beta-cellobiose were studied in vacuo through gradient geometry optimization using B3LYP density functionals and the 6-311++G** basis set. The conformationally dependent geometry changes and energies were explored as well as the hydrogen-bonding network. The lowest electronic energy structures found were not those suggested from available crystallographic and NMR solution data, where the glycosidic dihedral angles fall in the region (phi, psi) approximately (40 degrees, -20 degrees ). Rather, 'flipped' conformations in which the dihedral angles are in the range (phi, psi) approximately (180 degrees, 0 degrees ) are energetically more stable by approximately 2.5 kcal/mol over the 'experimentally accepted' structure. Further, when the vibrational free energy, deltaG, obtained from the calculated frequencies, is compared throughout the series, structures with (phi, psi) in the experimentally observed range still have higher free energy ( approximately 2.0 kcal/mol) than 'flipped' forms. The range of bridging dihedral angles of the 'normal' conformers, resulting from the variance in the phi dihedral is larger than that found in the 'flipped' forms. Due to this large flat energy surface for the normal conformations, we surmise that the summation of populations of these conformations will favor the 'normal' conformations, although evidence suggests that polar solvent effects may play the dominant role in providing stability for the 'normal' forms. Even though some empirical studies previously found the 'flipped' conformations to be lowest in energy, these studies have been generally discredited because they were in disagreement with experimental results. Most of the DFT/ab initio conformations reported here have not been reported previously in the ab initio literature, in part because the use of less rigorous theoretical methods, i.e. smaller basis sets, have given results in general agreement with experimental data, that is, they energetically favored the 'normal' forms. These are the first DFT/ab initio calculations at this level of theory, apparently because of the length and difficulty of carrying out optimizations at these high levels.     

Aldol additions with mutant lipase: analysis by experiments and theoretical calculations

A Ser105Ala mutant of Candida antarctica lipase B has previously been shown to catalyze aldol additions. Quantum chemical calculations predicted a reaction rate similar to that of natural enzymes, whereas experiments showed a much lower reaction rate. Molecular dynamics simulations, presented here, show that the low reaction rate is a consequence of the low frequencies of near attack complexes in the enzyme. Equilibrium was also considered as a reason for the slow product formation, but could be excluded by performing a sequential reaction to push the reaction towards product formation. In this paper, further experimental results are also presented, highlighting the importance of the entire active site for catalysis.     

Ab initio and DFT study on the electrophilic addition of bromine to endo-tricyclo[3.2.1.02,4]oct-6-ene

Full geometric optimization of endo-tricyclo[3.2.1.0^2,4]oct-6-ene (endo-TCO) by ab initio and DFT methods allowed us to investigate the structure of the molecule. The double bond is endo-pyramidalized and its two faces are no longer found to be equivalent. The exo face of the double bond has regions with far more electron density (q_i,HOMO) and more negative electrostatic potential. The endo-TCO-Br₂ system was investigated at the B3LYP/6-311+G** level and the endo-TCO···Br₂(exo) molecular complex was found to be relatively more stable than the endo-TCO···Br₂(endo) complex. The cationic intermediates of the reaction were studied by ab initio and DFT methods. The bridged exo-bromonium cation(I) is relatively more stable than the endo-bromonium cation(II). An absolute exo-facial selectivity should be observed in the addition reaction of Br₂ to endo-TCO, which is caused by steric and electronic factors. The nonclassical rearranged cation IV was found to be the most stable ion among the cationic intermediates and the ionic addition occurs via the formation of this cation. The mechanism of the addition reaction is also discussed.     

Potential transition-state analogs for glycosyltransferases. Design and DFT calculations of conformational behavior

The structure of a previously calculated transition state (TS) was used to design the [tetrahydro-2-(methylthio)furan-2-yl]methyl phosphate dianion (1) as a new scaffold for transition-state analogs of reactions catalyzed by the inverting glycosyltransferases. This scaffold contains relevant features of the donor and acceptor and represents a new type of potential inhibitors for these enzymes. Available conformational space of 1 was explored using DFT quantum chemical methods by means of two-dimensional potential-energy maps calculated as a function of Phi, Psi, and omega dihedral angles at the B3LYP/6-31+G* level. The calculated potential energy surfaces revealed the existence of several low-energy domains. Structures from these regions were refined at the 6-311++G** level and led to 14 conformers. The stability of conformers is influenced by their environment, and in aqueous solution two conformers dominate the equilibrium. A superposition of calculated conformers with the predicted TS structure revealed that the preferred conformers in solution nicely mimic structural features of the TS. These results imply that 1 has structural properties required to mimic the TS and therefore can be used as a scaffold for further development of TS-analog inhibitors for retaining glycosyltransferases.     

The ethylene/metal(0) and ethylene/metal(I) redox system: model ab initio calculations

Ab initio calculations (coupled cluster with single and double excitations; CCSD) have been used to investigate the model redox systems ethylene:M(0) (M = Li, Na, K, Rb, Cs) and ethylene:M(I) (M = Be, Mg, Ca, Sr, Ba, Zn, Cd, Hg). Within C2v symmetry, the ground (2A1) states correspond to the charge distribution given in the title. The lowest (2B2) excited states correspond, somewhat counter intuitively, to the ethylene*-/=M(II)ion pair. These trends can be rationalized on the basis of simple electrostatic and configuration-mixing arguments that lead to two simple equations for predicting the electron-transfer energies for oxidation or reduction of the ethylene. The electron-transfer energies to the 2B2 ion pairs are dominated by the electrostatic ion-pairing energies.