μ-H-Bridged Bicyclo[3.3.3]undecyl Cations. Theoretical Calculations of Physical and Chemical Properties

7-H-Bridged carbocations 1 and 2, which are still unknown experimentally, are structures with fascinating possibilities as intermediates for the synthesis of very strained in-bicyclic and tricyclic alkanes and alkenes. They are also expected to possess record high pK_a values. In conjunction with our experimental program to try to prepare 1 and 2, we have carried out ab initio calculations on these structures and various reference compounds, with the aim of assessing just how stable these cations might be, and what physical and chemical properties they might possess. The results of these studies confirm that 1 and 2 should be viable species; they have energies similar to those of the conventional out-cations, and the 7-H bond distances are not very different from those calculated for known 7-H cations. The calculated ¹H NMR chemical shift for the mu-H of 1 is -12 - 0.5 and -9.5 - 0.5 for 2, both values considerably more negative than in known 7-H cations. The possible effect of large amplitude motions of the 7-H on the ¹H NMR chemical shift was investigated and not found to be significant. The pK_as for 1 and 2 are estimated to be 17-18 with respect to an alkene conjugate base, a virtually unimaginable size for a formally alkyl cation. The paper also discusses the possibility of the 7-H being involved in the acid-conjugate base chemistry, since this is shown to be a hugely exothermic reaction. Finally, the alkenes and alkanes associated with cations 1 and 2 have been calculated, the in-alkene 7 from cation 1 is shown, for example, to possess a large steric strain, yet this structure should be accessible via deprotonation of 1 with a strong base.     

QM/MM model study on properties and structure of some antibiotics in gas phase: Comparison of energy and NMR chemical shift

The combination of Quantum Mechanics (QM) and Molecular Mechanics (MM) methods has become an alternative tool for many applications for which pure QM and MM are not suitable. The QM/MM method has been used for different types of problems, for example: structural biology, surface phenomena, and liquid phase. In this paper, we have used these methods for antibiotics and then we compared results. The calculations were done by the full ab initio method (HF/3-21G) and the (HF/STO-3G) and QM/MM (ONIOM) method with HF (3-21G)/AM1/UFF and HF (STO-3G)/AM1/UFF. We found the geometry obtained by the QM/MM method to be very accurate, and we can use this rapid method in place of time consuming ab initio methods for large molecules. Comparison of energy values in the QM/MM and QM methods is given. In the present work, we compare chemical shifts and conclude that the QM/MM method is a perturbed full QM method. The work has been done on penicillin, streptomycin, benzyl penicillin, neomycin, kanamycin, gentamicin, and amoxicillin.     

Ab initio study of singlet excited states of bicyclo[2.2.0]hexasilane and tricyclo[4.2.0.02,5]octasilane

The singlet excited states in the optimized geometries of bicyclo[2.2.0]hexasilane and tricyclo[4.2.0.0^2,5]octasilane are studied theoretically using the ab initio molecular orbital method at the RHF/3-21G^* level with the all-singles CI approximation. These molecules are found to have zigzag structures in both the ground states and the singlet excited states corresponding to the lowest absorptions, and the estimated Stokes shifts between the lowest absorption and fluorescence are similar to the experimental values.     

Ab Initio Calculations of Vibrational Frequencies,Potential Functions of Internal Rotations and Vibrational Infrared and Raman Spectra for 3,3,3-Trifluoropropanal

The conformational behavior and structure of 3,3,3,-trifluoropropal have been investigated by utilizing ab initio calculations with the 6-31G^** basis set (valence double zeta basis with polarization functions on all atoms) at the restricted Hartree Fock (RHF), second-order Møller-Plesset perturbation (MP2), and Density Functional (B3LYP) levels. The molecule is predicted to have a cis Û gauche conformational equilibrium. Full optimization of the transition states was performed and the rotational barriers of both the CHO and CF₃ rotors were calculated. Vibrational frequencies were computed at the three levels and the zero-point corrections were included into the calculated asymmetric CHO rotational barrier. Complete vibrational assignments were made on the basis of normal coordinate calculations for both stable conformers of the molecule.     

Study of the Tautomerism by Experimentally and Theoretically Estimated 13C and 15N Chemical Shifts

2-Substituted 5-Me-7OH-1,2,4-Triazolo[1,5-a]pyrimidines can exist as different tautomeric forms. The tautomeric equilibrium of these compounds were determined by various NMR spectroscopic methods and quantum-chemical calculations. The tautomeric equilibria of 2-substituted 1,2,4-Triazolopyrimidines depend on the used solvent. In order to take solvent effects into account, ab initio calculations using the SCI-PCM method were carried out. The solvation energy depends on the polarity of the substituents in position 2. The comparison of chemical shifts determined by experimental methods and theoretical ab initio methods were used to definitely find out the the tautomeric equilibria of these compounds.     

A Detailed Study of VESPA Electrostatic Potential-Derived Atomic Charges

VESPA, an improved semiempirical method for the calculation of electrostatic potential-derived atomic charges has been tested. It is shown that this approach is even less dependent upon molecular orientation than "high density" CHELPG ab initio ESP-derived charges. The conformational dependence of VESPA charges has been investigated for rotation around the C-N bond in formamide and 11 different conformers of glycerolphosphorylcholine. The results obtained are also compared to the corresponding ab initio values. Finally, VESPA is used to calculate electrostatic potential-derived charges for bioorganic molecules. We discuss the abilities and the limitations of ESP charges in this area.     

Evaluating amber force fields using computed NMR chemical shifts

NMR chemical shifts can be computed from molecular dynamics (MD) simulations using a template matching approach and a library of conformers containing chemical shifts generated from ab initio quantum calculations. This approach has potential utility for evaluating the force fields that underlie these simulations. Imperfections in force fields generate flawed atomic coordinates. Chemical shifts obtained from flawed coordinates have errors that can be traced back to these imperfections. We use this approach to evaluate a series of AMBER force fields that have been refined over the course of two decades (ff94, ff96, ff99SB, ff14SB, ff14ipq, and ff15ipq). For each force field a series of MD simulations are carried out for eight model proteins. The calculated chemical shifts for the ¹H, ¹⁵N, and ¹³C^a atoms are compared with experimental values. Initial evaluations are based on root mean squared (RMS) errors at the protein level. These results are further refined based on secondary structure and the types of atoms involved in nonbonded interactions. The best chemical shift for identifying force field differences is the shift associated with peptide protons. Examination of the model proteins on a residue by residue basis reveals that force field performance is highly dependent on residue position. Examination of the time course of nonbonded interactions at these sites provides explanations for chemical shift differences at the atomic coordinate level. Results show that the newer ff14ipq and ff15ipq force fields developed with the implicitly polarized charge method perform better than the older force fields.     

Molecular Parameterisation and the Theoretical Calculation of Electrode Potentials

The difference in reduction potentials between ortho and para-benzoquinones has been calculated. The employs gas phase ab initio and semi-empirical computations in combination with free energy perturbation theory applied to gas and solution phase Monte Carlo simulations. The effects on calculated results of altering solute electrostatic parameterisation in solution phase simulations is examined. Atom centred charges derived from the molecular electrostatic potentials, MEPs, from optimised ab initio wavefunctions and charges generated by consideration of hydrogen bonded complexes are considered. Parameterisation of hydroxyl torsions in hydroquinone molecules is treated in a physically realistic manner. The coupled torsional system of the ortho-hydrobenzoquinone molecule is described by a potential energy surface calculated using gas phase AM1 semi-empirical computations rather than the simple torsional energy functions frequently employed in such calculations. Calculated differences in electrode potentials show that the electrostatic interactions of quinone and hydroquinone molecules in aqueous solution are not well described by atom centred charges derived from ab initio calculated MEPs. Moreover, results in good agreement with the experimental reduction potential difference can be obtained by employing high level ab initio calculations and solution phase electrostatic parameters developed by consideration of hydrogen bonded complexes.     

Vibrational assignments and derived potential energy distributions for tri- and difluoromethyl ketene by density functional calculations

The structures of 3,3,3-trifluoromethyl ketene and 3,3-difluoromethyl ketene were studied by utilizing ab initio calculations with the 6-311++G** basis set at the (B3LYP) Density Functional level. Full optimization was performed for both molecules in their ground and transition states. Energy optimization of the systems under investigation shows that trifluoromethyl ketene exists only in the cis conformation (fluorine atom eclipses the ketene group). Difluoromethyl ketene was predicted to have two stable conformations: the cis (hydrogen atom eclipses the ketene group) and the gauche (fluorine atom eclipses the ketene group) form. The conformational stability of the molecules was found to be governed mainly by electrostatic and molecular orbital interactions. The vibrational frequencies were computed and complete assignments were provided on the basis of normal coordinate calculations and comparison with similar molecules. The potential energy distributions (PED) among symmetry coordinates were derived for the stable conformations of the two molecules.     

Modelling the interactions of protein side-chains

The study of small model molecules containing the relevant functional groups can help us to understand the interactions between side-chains in proteins.Ab initio quantum chemical techniques allow the interactions between the model molecules to be studied with much greater accuracy than is possible for an entire protein, where the use of simple empirical potentials is the norm. In particular, the use ofab initio methods on model molecules permits us to incorporate the atom-atom anisotropic directionality of these interactions. We survey various methods of obtaining the components of theab initio interaction energy. These are then applied to three systems of biological interest. The first of these is the arginine/aspartate pair found in salt bridges, which involves hydrogen bonding between two charged species. Secondly, we look at the arginine/phosphotyrosine interaction found in complexes between SH2 domains and peptide ligands: here we find that the arginine/phosphate part of the interaction is energetically far more important than the arginine/aromatic part. Finally, we describe a detailed study of amino/aromatic interactions in proteins: unconventional hydrogen bonds are found to be remarkably uncommon relative to stacked geometries, and the reasons for this are examined.     

New potential model for molecular dynamic simulation of liquid HF. I—Parameter optimization for charge equilibration method

In order to build a complete potential model to perform classical molecular dynamic simulations of liquid HF, a new optimization method is proposed to obtain transferable parameters for charge equilibration method on the basis of ab initio reference data. The optimized parameters (the electronegativity χ and the Slater orbital exponent ζ for H and F atoms) appear to be able to reproduce the variations of the electrostatic potential calculated from an ab initio method in a liquid phase of HF molecules for different thermodynamic conditions. It is concluded that the proposed method is general, precise and efficient to obtain transferable and realistic parameters.     

Applicability of PM3 to transphosphorylation reaction path: Toward designing a minimal ribozyme

A growing body of evidence shows that RNA can catalyze many of the reactions necessary both for replication of genetic material and the possible transition into the modern protein-based world. However, contemporary ribozymes are too large to have self-assembled from a prebiotic oligonucleotide pool. Still, it is likely that the major features of the earliest ribozymes have been preserved as molecular fossils in the catalytic RNA of today. Therefore, the search for a minimal ribozyme has been aimed at finding the necessary structural features of a modern ribozyme (Beaudry and Joyce, 1990). Both a three-dimensional model and quantum chemical calculations are required to quantitatively determine the effects of structural features of the ribozyme on the reaction it catalyzes. Using this model, quantum chemical calculations must be performed to determine quantitatively the effects of structural features on catalysis. Previous studies of the reaction path have been conducted at theab initio level, but these methods are limited to small models due to enormous computational requirements. Semiempirical methods have been applied to large systems in the past; however, the accuracy of these methods depends largely on the system under investigation. In the preent study we assess the validity of the MNDO/PM3 method on a simple model of the ribozyme-catalyzed reaction, or hydrolysis of phosphoric acid. We find that the results are qualitatively similar toab initio results using large basis sets. Therefore, PM3 is suitable for studying the reaction path of the ribozyme-catalyzed reaction.     

Modeling of Supramolecular Properties of Molecular Tweezers, Clips, and Bowls

The electrostatic potential surface (EPS) is calculated for molecular tweezers, clips, and bowls at different levels of theory (semiempirical AM1, ab initio HF/6-31G*, and density functional theory pBP/DN**). According to these calculations, the molecular electrostatic potential (MEP) on the concave side of the molecular tweezers and clips is suprisingly negative for hydrocarbons. This finding seems to be a general phenomenon in nonconjugated ?-electron systems with concave-convex topology and it explains the receptor properties of the molecular tweezers and clips. Analogous calculations performed for the conjugated aromatic molecular bowls show different results. The DFT calculations predict that in these systems the more negative MEP lies on the concave side similar to the findings for the nonconjugated molecular tweezer- and clip-systems, whereas the AM1 calculation leads to the opposite result that the MEP is more negative on convex side of the bowl-systems.     

Neural networks as a tool for compact representation of ab initio molecular potential energy surfaces

Ab initio quantum chemical calculations of molecular properties such as, e.g., torsional potential energies, require massive computational effort even for moderately sized molecules, if basis sets with a reasonable quality are employed. Using ab initio data on conformational properties of the cofactor (6R,1′R,2′S)-5,6,7,8-tetrahydrobiopterin, we demonstrate that error backpropagation networks can be established that efficiently approximate complicated functional relationships such as torsional potential energy surfaces of a flexible molecule. Our pilot simulations suggest that properly trained neural networks might provide an extremely compact storage medium for quantum chemically obtained information. Moreover, they are outstandingly comfortable tools when it comes to making use of the stored information. One possible application is demonstrated, namely, computation of relaxed torsional energy surfaces.     

Homodesmotic reactions in helicene and phenacene molecules

Helicene molecules were analysed on the basis of their intrinsic aromaticity, and compared with the corresponding phenacene. The analysis of aromaticity was performed by homodesmotic reactions, and by the nucleus independent chemical shifts (NICS) index in the centre of the aromatic rings as well as in the centre of the helix. The results are very interesting, because the NICS shows that there is a strong antiaromatic zone in the centre of the molecule, and a strong aromatic zone in the strip. Therefore, these molecules represent a medley of electronic effects.     

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.     

Theoretical studies on radical formation in the interaction of cysteine with dicarbonyl compounds of biological relevance

A possible pathway for the interaction between cysteine and dicarbonyl compounds of glyoxal and methylglyoxal type was studied by quantum chemical methods (INDO,ab initio). The condensation reaction is likely to occur through intermediate products, formation of which competes with the dimerization reaction. Results fromab initio UHF calculation of Fermi contact interaction for the radical cation of the final product suggest an assignment of the hyperfine coupling constants for protons that differs from the one deduced from the electron spin resonance (ESR) spectrum.     

Methane in Water: An Ab Initio Study

Abstract

In preceding publications we discussed some properties of pure water in condensed phases using an ab initio approach. Here this study is used as a basis of comparison for analysing the behaviour of water as a solvent in the presence of an apolar molecule. Our analysis is focused on the process of organization of the hydrogen bonding network around the solute. For this purpose we perform some ab initio calculations for a system of 32 water molecules and one methane molecule at 300 K; in particular, the average molecular dipole moment of water is determined and the result is compared with that of pure water. Next the attention is switched to the methane molecule; related properties such as excluded volume and sphericity of its shape are illustrated and discussed. A comparison with results obtained using classical approaches suggests that some classical models of water can be considered to be still valid when they are used to analyse the water-methane system.     

Aromaticity of graphene nanoflakes in a new way: fragment analysis by combination of the nucleus-independent chemical shifts and the anisotropy of current induced density

A graphene nanoflake (GNF) is a polycyclic aromatic hydrocarbon (PAH) with a huge two-dimensional π-conjugated carbon material in which a central benzene ring is surrounded by identical benzene-type rings through infinite alternant method. In this paper, we explore the structure-aromaticity relationship of the GNFs and the GNFs with hollow sites (GNFHs) by combining the nucleus-independent chemical shifts (NICS) with the anisotropy of the current induced density (ACID). Firstly, the benzene is a typical aromatic molecule (NICS = ?9.671 ppm), GNFs 1-6 is darned with benzene and the corresponding GNFHs 1′-6′. Secondly, the NICS values of GNFs 1-6 alternately vary: ?1.214 (1) > ?13.847 (2) < ?2.662 (3) > ?14.530 (4) < ?3.932 (5) > ?13.978 (6) ppm, the GNFs (2, 4, 6) with even fragments of annulene have larger aromaticity than that of GNFs (1, 3, 5) with odd fragments of annulene. Significantly, the NICS values of GNFs 1-6 can also be fragment analyzed by the NICS values and ACID of benzene and corresponding GNFHs 1′-6′. The NICS values for GNFs (2, 4, 6) can be roughly estimated by the NICS value of benzene minus the NICS value of the GNFHs (2′, 4′, 6′), respectively. The NICS values for GNFs (1, 3, 5) can be roughly estimated by the NICS value of the GNFHs (1′, 3′, 5′) minus the NICS value of benzene, respectively. We hope that the present work can provide a simple and reliable method for the rational design of the GNF with aromaticity, which may be used to understand the origin of the graphene nanoflake aromatic properties.