Search

The interactions between the aromatic portion of the fluorinated n-(4-sulfamylbenzoyl)benzylamine (SBB) inhibitors and two residues of Human Carbonic Anhydrase II (HCAII)- Phe-131 and Pro-202 are studied. The structure of proteins is determined by the interactions between aromatic rings.

Potential energy curves are produced for the halogen bonding interactions of several halobenzene-formaldehyde complexes. The results have shown that for most halogen substituents, a halobenzene and formaldehyde form stable halogen bonded complexes with interaction energies that increase as the size of the halogen substituent increases.

A quantum description is used to find the time limit for balancing an idealized pencil-like object on end. In agreement with some prior studies, analysis for this system shows that quantum effects are not observable in any foreseeable circumstances, either by casual experimentation or by extensive laboratory preparation. A direct solution of Schrodinger’s equation avoids an a priori use of the Heisenberg uncertainty relation in the classical equations of motion, which, although very much a proper usage, may lead to misunderstanding of the results. The classical equations of motion are adequate for the pencil in all circumstances. [ABSTRACT FROM AUTHOR]

A study was conducted to determine the relative magnitudes of the various interactions that occur between different steroid hormones and residues found within the binding pocket of mutated mineralocorticoid (MR). The results obtained revealed a strong hydrogen bond between progesterone and Thr945 and a relatively strong hydrophobic interaction between progesterone and Asn770.

The performance of the MP2 method, when paired with several different medium and extended basis sets, is assessed for the accurate computations of binding energies of hydrogen bonded and dispersion bound biologically derived complexes. It is shown that generally the MP2 technique, when paired with any basis set, does not yield reliable results for cyclic hydrogen bonds such as those seen in nucleic acid base pairs.

The effects of solvation on the stability of the hydrophobic core of the protein rubredoxin are evaluated. The results have indicated that short-range interactions between amino acid side chains are among the forces that contribute to the stability of rubredoxin and the solvation plays a pronounced role in the overall stability of the protein's hydrophobic core.

Potential energy curves for the interaction energies of a set of edge-to-face fluorine substituted benzene dimers is studied in an attempt to clarify the counterintuitive role of fluorination on the aromatic interactions found within the N-(4-sulfamylbenzoyl)benzylamine-Human Carbonic Anhydrase II (SBB-HCAII) complex. However, findings do not explain the crystallographic findings for the SBB-HCAII protein-ligand complex, where increased fluorination resulted in closer edge-to-face contacts, suggesting that there are factors, other than edge-to-face aromatic interactions, influencing the system's behavior.

The pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCA II) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) are calculated using semiempirical quantum mechanics based methods. The interaction between the ligand and the protein is dissected by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution.

The synthesis and crystal structures of the isomeric molecular salts 2-, 3- and 4-cyano-1-methylpyridinium hexafluoridophosphate, C7H7N2 +·PF6-, are reported. In 2-cyano-1-methylpyridinium hexafluoridophosphate, C--H...F hydrogen bonds form chains extending along the c-axis direction, which are associated through C--H...F hydrogen bonds and P--F...π(ring) interactions into stepped layers. For 3-cyano-1-methylpyridinium hexafluoridophosphate, corrugated sheets parallel to [001] are generated by C--H...F hydrogen bonds and P--F...π(ring) interactions. The sheets are weakly associated by a weak interaction of the cyano group with the six-membered ring of the cation. In 4-cyano-1-methylpyridinium hexafluoridophosphate, C--H...F hydrogen bonds form a more open three-dimensional network in which stacks of cations and of anions are aligned with the b-axis direction. Dispersion-corrected density functional theory (DFT-D) calculations were carried out in order to elucidate some of the energetic aspects of the solid-state structures. The results indicate that the distribution of charge within a molecular ionic cation can play a large role in determining the strength of a cation-anion interaction within a crystal structure. Crystals of 2-cyano-1-methylpyridinium hexafluoridophosphate are twinned by a 180° rotation about the c* axis. The anion in 3-cyano-1-methylpyridinium hexafluoridophosphate is rotationally disordered by 38.2 (1)° in an 0.848 (3):0.152 (3) ratio. [ABSTRACT FROM AUTHOR]

Halogen bonds involving cationic halogen bond donors and anionic halogen bond acceptors have recently been recognized as being important in stabilizing the crystal structures of many salts. Theoretical characterization of these types of interactions, most importantly in terms of their directionality, has been limited. Here we generate high-quality symmetry adapted perturbation theory potential energy curves of a H3N–C≡C–Br+…Cl− model system in order to characterize halogen bonds involving charged species, in terms of contributions from electrostatics, exchange, induction, and dispersion, with special emphasis on analyzing contributions that are most responsible for the directionality of these interactions. It is found that, as in the case of neutral halogen bonds, exchange forces are important contributors to the directionality of charged halogen bonds, however, it is also found that induction effects, which contribute little to the stability and directionality of neutral halogen bonds, play a large role in the directionality of halogen bonds involving charged species. Potential energy curves based on the ̉B97X-D/def2-TZVP/C-PCM method, which includes an implicit solvation model in order to mimic the effects of the crystal medium, are produced for both the H3N–C≡C–Br+…Cl− model system and for the 4-bromoanilinium…Cl− dimer, which is based on the real 4-bromoanilinium chloride salt, whose crystal structure has been determined experimentally. It is found that, within a crystal-like medium, charged halogen bond are significantly weaker than in the gas phase, having optimum interaction energies up to approximately −20 kcal mol−1. [ABSTRACT FROM AUTHOR]

Here, we investigate the strengths of R-X···π interactions, involving both chlorine and bromine, in model systems derived from protein-ligand complexes found in the PDB. We find that the strengths of these interactions can vary significantly, with binding energies ranging from -2.01 to -3.60 kcal/mol. Symmetry adapted perturbation theory (SAPT) analysis shows that, as would be expected, dispersion plays the largest role in stabilizing these R-X···π interactions, generally accounting for about 50% to 80% of attraction. R-Br···π interactions are, for the most part, found to be stronger than R-Cl···π interactions, although the relative geometries of the interacting pair and the halogen's chemical environment can also have a strong impact. The two factors that have the strongest impact on the strength of these R-X···π interactions is the distance between the halogen and the phenyl plane as well as the size of the halogen σ-hole. [ABSTRACT FROM AUTHOR]

Background: While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs).Purpose: To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs.Study Design: Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined.Methods: The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed.Results: In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation.Conclusion: The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis. [ABSTRACT FROM AUTHOR]

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain. [ABSTRACT FROM AUTHOR]

Halogen bonds involving an aromatic moiety as an acceptor, otherwise known as R−X⋅⋅⋅π interactions, have increasingly been recognized as being important in materials and in protein-ligand complexes. These types of interactions have been the subject of many recent investigations, but little is known about the ways in which the strengths of R−X⋅⋅⋅π interactions vary as a function of the relative geometries of the interacting pairs. Here we use the accurate CCSD(T) and SAPT2+3δMP2 methods to investigate the potential energy landscapes for systems of HBr, HCCBr, and NCBr complexed with benzene. It is found that only the separation between the complexed molecules have a strong effect on interaction strength while other geometric parameters, such as tilting and shifting R−Br⋅⋅⋅π donor relative to the benzene plane, affect these interactions only mildly. Importantly, it is found that the C6 v (T-shaped) configuration is not the global minimum for any of the dimers investigated. [ABSTRACT FROM AUTHOR]

High quality CCSD(T) and DFT-SAPT potential energy curves were generated for complexes of HCN, BrCN, and HBr donors with formaldehyde and benzene acceptors in order to compare the strengths and properties of hydrogen bonds, halogen bonds, C H⋯π interactions, and C Br⋯π interactions. It is found that interactions involving BrCN, which has a large region of positive charge, are similar in strength to interactions involving HCN. Dispersion plays a pronounced role in Y Br⋯π complexes, accounting for about two thirds of attraction in the HBr⋯C 6 H 6 complex. As might be expected, interactions involving halogens have stronger contributions from dispersion. [ABSTRACT FROM AUTHOR]

In this work we highlight recent work aimed at the characterization of halogen bonds. Here we discuss the origins of the σ-hole, the modulation of halogen bond strength by changing of neighboring chemical groups (i.e. halogen bond tuning), the performance of various computational methods in treating halogen bonds, and the strength and character of the halogen bond, the dihalogen bond, and two hydrogen bonds in bromomethanol dimers (which serve as model complexes) are compared. Symmetry adapted perturbation theory analysis of halogen bonding complexes indicates that halogen bonds strongly depend on both dispersion and electrostatics. The electrostatic interaction that occurs between the halogen σ-hole and the electronegative halogen bond donor is responsible for the high degree of directionality exhibited by halogen bonds. Because these noncovalent interactions have a strong dispersion component, it is important that the computational method used to treat a halogen bonding system be chosen very carefully, with correlated methods (such as CCSD(T)) being optimal. It is also noted here that most forcefield-based molecular mechanics methods do not describe the halogen σ-hole, and thus are not suitable for treating systems with halogen bonds. Recent attempts to improve the molecular mechanics description of halogen bonds are also discussed. [ABSTRACT FROM AUTHOR]

For many years, MP2 served as the principal method forthe treatmentof noncovalent interactions. Until recently, this was the only techniquethat could be used to produce reasonably accurate binding energies,with binding energy errors generally below ∼35%, at a reasonablecomputational cost. The past decade has seen the development of manynew methods with improved performance for noncovalent interactions,several of which are based on MP2. Here, we assess the performanceof MP2, LMP2, MP2-F12, and LMP2-F12, as well as spin component scaledvariants (SCS) of these methods, in terms of their abilities to produceaccurate interaction energies for binding motifs commonly found inorganic and biomolecular systems. Reference data from the newly developedS66 database of interaction energies are used for this assessment,and a further set of 38 complexes is used as a test set for SCS methodsdeveloped herein. The strongly basis set-dependent nature of MP2 isconfirmed in this study, with the SCS technique greatly reducing thisbehavior. It is found in this work that the spin component scalingtechnique can effectively be used to dramatically improve the performanceof MP2 and MP2 variants, with overall errors being reduced by factorsof about 1.5–2. SCS versions of all MP2 variants tested hereare shown to give similarly accurate overall results. [ABSTRACT FROM AUTHOR]

Dissociation curves calculated using multiple correlated QM methods for 66 noncovalent complexes (Řezáč et al., J Chem Theory Comput 2011, 7, 2427) have allowed us to interpolate equilibrium intermolecular distances for each studied method. Comparison of these data with CCSD(T)/complete basis set reference geometries provides information on how these methods perform in geometry optimizations. The large set of systems considered here is necessary for reliable statistical evaluation of the results and assessment of the robustness of the studied methods. Our results show that advanced methods such as MP3 and CCSD provide significant improvement over MP2 only when empirical scaling is used. The best results can be achieved with spin component scaled CCSD optimized for noncovalent interactions, with a root mean square error of 0.4% of the equilibrium distance. Scaled MP3, the MP2.5 method, yields comparably good results (error 0.5%) while being substantially cheaper. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2012 [ABSTRACT FROM AUTHOR]

In this work, we study the hydrogen bonds (H-bonds) involving hydroxyl and amino groups bonded to phenyl and pyrimidine rings (as H-bond donors). These types of interactions play important roles in the recognition of ligands by proteins and are also important in the design of materials. The effects of aromatic fluorine substitutions on aromatic rings are also investigated, and it is found that these substitutions can have large effects on the hydrogen bonding interactions that occur in our model systems, making them substantially stronger. This finding offers a new mechanism for the modification of these types of interactions, potentially opening new paths in the design of novel pharmaceuticals and materials. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [ABSTRACT FROM AUTHOR]

The addition of a directional term to standard Jastrow functions was investigated in variational quantum Monte Carlo calculations for the LiH molecule using wavefunctions composed of Slater determinants combined with Pade´ and with Schmidt–Moskowitz functions. The recovery of correlation energy was improved significantly by the added term: from 52% to 71% for the Pade´ function and from 61% to 78% for the Schmidt–Moskowitz function. [Copyright &y& Elsevier]

We have repeated previous calculations on the potential energy surface for the reaction H+H[sub 2]→H[sub 2]+H using Green function diffusion Monte Carlo methods. The barrier height obtained in the new calculations is 9.608±0.001 kcal/mol. Calculations were also made near the Jahn-Teller Cusp and the van der Waals minimum. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We have developed a new method for calculating configuration interaction coefficients for trial wavefunctions used in quantum Monte Carlo calculations of molecular structure. These numerical calculations can be carried out with optimized Jastrow functions included in the wavefunction. These calculations produce coefficients different from those obtained through methods using analytical integration without the Jastrow functions and lead to more accurate trial wavefunctions. We tested the method on the beryllium atom and found that the VMC energy obtained with improved coefficients (-14.6615 hartrees) was 0.9 millihartrees lower than the energy obtained using coefficients from analytical calculations (-14.6606 hartrees). This energy difference corresponds to about 1% of the correlation energy. [ABSTRACT FROM AUTHOR]

One of the main challenges for the future hydrogen economy is finding a safe and efficient way to store hydrogen. Materials with large surface areas, like carbon nanotubes and their analogues boron-nitride nanotubes, are being studied as potential candidates for this purpose. We perform density functional theory (DFT) and dispersion-corrected DFT (DFT-D) calculations of the adsorption of molecular hydrogen on graphene and boron-nitride sheets and compare the results against Møller-Plesset perturbation theory (MP2 and MP2.5). Our results indicate that DFT underestimates the binding energies, while DFT-D gives a very good agreement with the higher-order theory. Within DFT-D, we show that the binding energy of molecular hydrogen to the outer walls of carbon nanotubes is more than 40% larger than that of boron-nitride nanotubes. [ABSTRACT FROM AUTHOR]

The synthesis and crystal structures of the isomeric mol-ecular salts 2-, 3- and 4-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C 7 H 7 N 2 + ·PF 6 - , are reported. In 2-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C-H⋯F hydrogen bonds form chains extending along the c -axis direction, which are associated through C-H⋯F hydrogen bonds and P-F⋯π(ring) inter-actions into stepped layers. For 3-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, corrugated sheets parallel to [001] are generated by C-H⋯F hydrogen bonds and P-F⋯π(ring) inter-actions. The sheets are weakly associated by a weak inter-action of the cyano group with the six-membered ring of the cation. In 4-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C-H⋯F hydrogen bonds form a more open three-dimensional network in which stacks of cations and of anions are aligned with the b -axis direction. Dispersion-corrected density functional theory (DFT-D) calculations were carried out in order to elucidate some of the energetic aspects of the solid-state structures. The results indicate that the distribution of charge within a mol-ecular ionic cation can play a large role in determining the strength of a cation-anion inter-action within a crystal structure. Crystals of 2-cyano-1-methyl-pyridinium hexa-fluorido-phosphate are twinned by a 180° rotation about the c * axis. The anion in 3-cyano-1-methyl-pyridinium hexa-fluorido-phosphate is rotationally disordered by 38.2 (1)° in an 0.848 (3):0.152 (3) ratio.

Aromatic systems contain both σ- and π-electrons, which in turn constitute σ- and π-molecular orbitals (MOs). In discussing the properties of these systems, researchers typically refer to the highest occupied and lowest unoccupied MOs, which are π MOs. The characteristic properties of aromatic systems, such as their low ionization potentials and electron affinities, high polarizabilities and stabilities, and small band gaps (in spectroscopy called the N → V1 space), can easily be explained based on their electronic structure. These one-electron properties point to characteristic features of how aromatic systems interact with each other. Unlike hydrogen bonding systems, which primarily interact through electrostatic forces, complexes containing aromatic systems, especially aromatic stacked pairs, are predominantly stabilized by dispersion attraction. The stabilization energy in the benzene dimer is rather small (~2.5 kcal/mol) but strengthens with heteroatom substitution. The stacked interaction of aromatic nucleic acid bases is greater than 10 kcal/mol, and for the most stable stacked pair, guanine and cytosine, it reaches approximately 17 kcal/mol. Although these values do not equal the planar H-bonded interactions of these bases (~29 kcal/mol), stacking in DNA is more frequent than H-bonding and, unlike H-bonding, is not significantly weakened when passing from the gas phase to a water environment. Consequently, the stacking of aromatic systems represents the leading stabilization energy contribution in biomacromolecules and in related nanosystems. Therefore stacking (dispersion) interactions predominantly determine the double helical structure of DNA, which underlies its storage and transfer of genetic information. Similarly, dispersion is the dominant contributor to attractive interactions involving aromatic amino acids within the hydrophobic core of a protein, which is critical for folding. Therefore, understanding the nature of aromatic interactions, which depend greatly on quantum mechanical (QM) calculations, is of key importance in biomolecular science. This Account shows that accurate binding energies for aromatic complexes should be based on computations made at the (estimated) CCSD(T)/complete basis set limit (CBS) level of theory. This method is the least computationally intensive one that can give accurate stabilization energies for all common classes of noncovalent interactions (aromatic-aromatic, H-bonding, ionic, halogen bonding, charge-transfer, etc.). These results allow for direct comparison of binding energies between different interaction types. Conclusions based on lower-level QM calculations should be considered with care.

We report the performance of composite post-MP2 ab initio methods with small basis sets for description of noncovalent interactions, using the S66 data set as a benchmark. For three representative complexes, it is shown that explicitly correlated coupled cluster (CCSD-F12a) methods yield interaction energies ca. 0.1 kcal/mol from the complete basis set limit with aug-cc-pVDZ. Triple excitations are not explicitly correlated in this approach, but we show that scaling the perturbative triples via the (T*) approximation improves agreement with benchmark values. Across the entire S66 data set, this approach results in a root-mean-square error (RMSE) of 0.13 kcal/mol or 3%, with well-balanced description of all classes of complex. The basis set dependence of traditional CCSD(T) interaction energies is examined, and the small 6-31G*(0.25) basis set is found to give particularly accurate results (RMSE = 0.15 kcal/mol, or 4%). We also employ spin component scaling (SCS) of CCSD-F12a data, which gives slightly better accuracy than CCSD(T*)-F12a if contributions from same- and opposite-spin pairs are optimized for this data set (RMSE = 0.08 kcal/mol, or 2%). Interpolation of local MP2 and MP3 is also shown to accurately reproduce benchmark data with both aug-cc-pVDZ (RMSE = 0.18 kcal/mol or 5%) and 6-31G*(0.25) (RMSE = 0.13 kcal/mol or 4%).

We present a set of 40 noncovalent complexes of organic halides, halohydrides, and halogen molecules where the halogens participate in a variety of interaction types. The set, named X40, covers electrostatic interactions, London dispersion, hydrogen bonds, halogen bonding, halogen-π interactions, and stacking of halogenated aromatic molecules. Interaction energies at equilibrium geometries were calculated using a composite CCSD(T)/CBS scheme where the CCSD(T) contribution is calculated using triple-ζ basis sets with diffuse functions on all atoms but hydrogen. For each complex, we also provide 10 points along the dissociation curve calculated at the CCSD(T)/CBS level. We use this accurate reference to assess the accuracy of selected post-HF methods.

Here we test the performance of the newly developed MP2.5 and MP2.X methods in terms of their abilities to generate accurate binding energies for noncovalently bound complexes at points away from their minimum energy structures and in terms of the accuracy of their potential energy minima. The MP2.X method is a scaled version of MP2.5 that allows for the use of smaller basis sets for the most computationally demanding (MP3) term, significantly reducing its computational cost. MP2.5 and MP2.X binding energy errors are compared to those of the reference CCSD(T)/CBS method on the dissociation curves associated with the S66 dataset of noncovalent complexes (S66x8). It is found that both the MP2.5 and MP2.X methods produce binding energy errors, as well as potential energy minima, that are significantly more accurate than those of MP2 methods. Thus, these methods are appropriate choices when very high quality geometries of noncovalent complexes are required.

In this article we present binding energy results for a scaled MP2.5 method along with several basis sets. The accuracy of the methods tested here is determined by comparison to reference data in the newly developed S66 data set of interaction energies. It is found that scaling of the MP2.5 correction term results in strongly improved binding energies for small basis sets, such as 6-31G* and 6-311++G**. The scaling parameter for larger basis sets, such as aug-cc-pVDZ and aug-cc-pVTZ, approaches a value of 0.50, which corresponds to the original (unparametrized) MP2.5 method. It is found that the MP2.X method yields S66 RMS errors of approximately 0.15 kcal mol(-1) for all basis sets. In addition to generally providing more accurate binding energies than MP2.5, MP2.X generally produces a more well-balanced description of noncovalent interactions, yielding better binding energies for dispersion-bound and mixed dispersion-electrostatic complexes.