Biomedical subjects

Peter Politzer

Publications and source records attributed to Peter Politzer.

12 recordsLinked to original sources

PubMed2006

An overview of halogen bonding.

Halogen bonding (XB) is a type of noncovalent interaction between a halogen atom X in one molecule and a negative site in another. X can be chlorine, bromine or iodine. The strength of the interaction increases in the order Cl<Br<I. After a brief review of experimental evidence relating to halogen bonding, we present an explanation for its occurrence in terms of a region of positive electrostatic potential that is present on the outermost portions of some covalently-bonded halogen atoms. The existence and magnitude of this positive region, which we call the sigma-hole, depends upon the relative electron-attracting powers of X and the remainder of its molecule, as well as the degree of sp hybridization of the s unshared electrons of X. The high electronegativity of fluorine and its tendency to undergo significant sp hybridization account for its failure to halogen bond. Some computed XB interaction energies are presented and discussed. Mention is also made of the importance of halogen bonding in biological systems and processes, and in crystal engineering.

Halogens↗

PubMed2006

Molecular surface electrostatic potentials and anesthetic activity.

General anesthetics apparently act through weak, noncovalent and reversible interactions with certain sites in appropriate brain proteins. As a means of gaining insight into the factors underlying anesthetic potency, we have analyzed the computed electrostatic potentials V (S)(r) on the surfaces of 20 molecules with activities that vary between zero and high. Our results are fully consistent with, and help to interpret, what has been observed experimentally. We find that an intermediate level of internal charge separation is required; this is measured by Pi, the average absolute deviation of V (S)(r), and the approximate window is 7 < Pi < 13 kcal mol(-1). This fits in well with the fact that anesthetics need to be lipid soluble, but also to have some degree of hydrophilicity. We further show that polyhalogenated alkanes and ethers, which include the most powerful known anesthetics, have strong positive potentials, V (S,max), associated with their hydrogens, chlorines and bromines (but not fluorines). These positive sites may impede the functioning of key brain proteins, for example by disrupting their normal hydrogen-bond patterns. It has indeed been recognized for some time that the most active polyhalogenated alkanes and ethers contain hydrogens usually in combination with chlorines and/or bromines.

Anesthetics↗

PubMed2006

Halogen bonding: the sigma-hole. Proceedings of "Modeling interactions in biomolecules II", Prague, September 5th-9th, 2005.

Halogen bonding refers to the non-covalent interactions of halogen atoms X in some molecules, RX, with negative sites on others. It can be explained by the presence of a region of positive electrostatic potential, the sigma-hole, on the outermost portion of the halogen's surface, centered on the R-X axis. We have carried out a natural bond order B3LYP analysis of the molecules CF(3)X, with X = F, Cl, Br and I. It shows that the Cl, Br and I atoms in these molecules closely approximate the [Formula: see text] configuration, where the z-axis is along the R-X bond. The three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of X, leaving the outermost region positive, the sigma-hole. This is not found in the case of fluorine, for which the combination of its high electronegativity plus significant sp-hybridization causes an influx of electronic charge that neutralizes the sigma-hole. These factors become progressively less important in proceeding to Cl, Br and I, and their effects are also counteracted by the presence of electron-withdrawing substituents in the remainder of the molecule. Thus a sigma-hole is observed for the Cl in CF(3)Cl, but not in CH(3)Cl.

Halogens↗

PubMed2006

Nonreactive molecular dynamics force field for crystalline hexahydro-1,3,5-trinitro-1,3,5 triazine.

An empirical nonreactive force field has been developed for molecular dynamics (MD)/Monte Carlo simulation of the formation, diffusion, and agglomeration of point defects in the crystal lattice of the alpha modification of hexahydro-1,3,5-trinitro-1,3,5 triazine (RDX) using flexible molecules. Bond stretching and angle bending are represented by Morse and harmonic functions, and torsion by a truncated cosine series. Nonbonded interactions, both inter- and intramolecular, are described by Buckingham potentials separately parametrized. Intermolecular electrostatic interactions are treated via a Coulomb term coupled with a smooth 15.0 A cutoff radius. Parameters were taken in part from earlier published works and were determined partly by fitting to known molecular and crystal properties of RDX. In MD simulations at constant pressure and temperature, the model was able to stabilize and maintain the correct crystal structure, symmetry, and molecular conformation of alpha-RDX. Vibrational frequencies, lattice binding energy and dimensions, coefficients of thermal expansion, and several unusually short intermolecular distances are all reproduced in satisfactory agreement with experimental data.

Journal Article↗

PubMed2006

Analysis of the reaction force for a gas phase S(N)2 process: CH3Cl + H2O --> CH3OH + HCl.

The "reaction force" F(R(c)) is the negative derivative of a system's potential energy V(R(c)) along the intrinsic reaction coordinate of a process. If V(R(c)) goes through a maximum, as is commonly the case, then F(R(c)) has a characteristic profile: a negative minimum followed by zero at the transition state and then a positive maximum. These features reflect four phases of the reaction: an initial one of reactant preparation, followed by two of transition to products, and then relaxation of the latter. In this study, we have analyzed, in these terms, a gas-phase S(N)2 substitution, selected to be CH3Cl + H2O --> CH3OH + HCl. We examine, at the B3LYP/6-31G level, the geometries, energetics, and molecular surface electrostatic potentials, local ionization energies, and internal charge separation.

Journal Article↗

PubMed2005

An unusual feature of end-substituted model carbon (6,0) nanotubes.

We have examined the effects of substituents on the computed electrostatic potentials V(S)(r) and average local ionization energies I(S)(r) on the surfaces of model carbon nanotubes of the types (5,5), (6,1) and (6,0). For the (5,5) and the (6,1), the effects upon both V(S)(r) and I(S)(r) of substituting a hydroxyl group at one end are primarily localized to that part of the system. For the (6,0) tube, however, a remarkable change is observed over its entire length, with V(S)(r) showing a marked gradation from strongly positive at the substituted end to strongly negative at the other; I(S)(r) correspondingly goes from higher to lower values. Replacing OH by another resonance- donor, NH2, produces similar results in the (6,0) system, while the resonance withdrawing NO2 does the opposite, but in equally striking fashion. We explain these observations by noting that the arrangement of the C-C bonds in the (6,0) tube facilitates charge delocalization over the full length and entire surface of the tube. Substituting NH2 and NO2 at opposite ends of the (6,0) tube greatly strengthens the gradations in both V(S)(r) and I(S)(r). The first hyperpolarizability of this system was found to be nine times that of para-nitroaniline, suggesting possible nonlinear optical applications. [figure: see text]. HF/STO-5G electrostatic potential on outer surface of open (6,0) C72H10NH2NO2. The nitro group is at the right end of the tube, the amino group at the left. In eV: purple is less than 14, blue is between 14 and 15, green is between 15 and 16.5, yellow is between 16.5 and 17.5, and red is more than 17.5.

Carbon↗

PubMed2004

Comparative analysis of surface electrostatic potentials of carbon, boron/nitrogen and carbon/boron/nitrogen model nanotubes.

We have extended an earlier study, in which we characterized in detail the electrostatic potentials on the inner and outer surfaces of a group of carbon and B(x)N(x) model nanotubes, to include several additional ones with smaller diameters plus a new category, C(2x)B(x)N(x). The statistical features of the surface potentials are presented and analyzed for a total of 19 tubes as well as fullerene and a small model graphene. The potentials on the surfaces of the carbon systems are relatively weak and rather bland; they are much stronger and more variable for the B(x)N(x) and C(2x)B(x)N(x). A qualitative correlation with free energies of solvation indicates that the latter two categories should have considerably greater water solubilities. The inner surfaces are generally more positive than the corresponding outer ones, while both positive and negative potentials are strengthened by increasing curvature. The outsides of B(x)N(x) tubes have characteristic patterns of alternating positive and negative regions, while the insides are strongly positive. In the closed C(2x)B(x)N(x) systems, half of the C-C bonds are double-bond-like and have negative potentials above them; the adjacent rows of boron and nitrogens show the usual B(x)N(x) pattern. When the C(2x)B(x)N(x) tubes are open, with hydrogens at the ends, the surface potentials are dominated by the B+-H- and N(-)-H+ linkages.

Boron↗

PubMed2004

Analysis of two intramolecular proton transfer processes in terms of the reaction force.

The negative derivative of the potential energy along an intrinsic reaction coordinate defines a force that has qualitatively a universal form for any process having an energy barrier: it passes through a negative minimum before the transition state, at which it is zero, followed by a positive maximum. We have analyzed two intramolecular proton transfer reactions in terms of several computed properties: internal charge separation, the electrostatic potentials of the atoms involved, their Fukui functions, and the local ionization energies. The variation of each of these properties along the intrinsic reaction coordinate shows a marked correlation with the characteristic features of the reaction force. We present a description of the proton transfer processes in terms of this force.

Journal Article↗

PubMed2004

Determination of noncovalent interaction energies from electronic densities.

Starting from the Hellmann-Feynman theorem, an expression is derived for the interaction energy in forming a noncovalently bound complex. It invokes only classical electrostatics, involving the charge distributions of the components as they are in the complex. We propose a method for obtaining these from the total charge distribution. Integration over the electronic densities is carried out by a numerical procedure slightly modified from that of Gavezzotti. We calculate the interaction energies for four molecular dimers at a variety of computational levels. The results are analyzed and compared to the best estimated values available in the literature.

Journal Article↗

PubMed2004

Calculation of electrostatic and polarization energies from electron densities.

We investigate procedures for calculating the electrostatic and polarization energies, Ees and Epol, associated with noncovalent interactions. The starting points are the electron densities of the isolated components and the complex; these could be obtained either computationally or experimentally. A slightly modified version of a scheme proposed by Gavezzotti is used to carry out numerical integrations over these electron densities. Our approach to estimating Epol is based upon partitioning the charge distributions of the components into overlapping and nonoverlapping regions. The effects of varying the integration parameters, computational techniques and basis sets are examined in detail for several noncovalently bound molecular dimers. Our results are in good agreement with the values of Ees and Epol produced by other methods, which require analytical integrations over interaction Hamiltonian matrix elements.

Journal Article↗

PubMed2003

Segmental analysis of molecular surface electrostatic potentials: application to enzyme inhibition.

We have recently shown that the anti-HIV activities of reverse transcriptase inhibitors can be related quantitatively to properties of the electrostatic potentials on their molecular surfaces. We now introduce the technique of using only segments of the drug molecules in developing such expressions. If an improved correlation is obtained for a given family of compounds, it would suggest that the segment being used plays a key role in the interaction. We demonstrate the procedure for three groups of drugs, two acting on reverse transcriptase and one on HIV protease. Segmental analysis is found to be definitely beneficial in one case, less markedly so in another, and to have a negative effect in the third. The last result indicates that major portions of the molecular surfaces are involved in the interactions and that the entire molecules need to be considered, in contrast to the first two examples, in which certain segments appear to be of primary importance. This initial exploratory study shows that segmental analysis can provide insight into the nature of the process being investigated, as well as possibly enhancing the predictive capability.

Algorithms↗

PubMed2003

Electrostatic potentials and covalent radii.

We begin with a brief overview of the electrostatic potential V(r) as a fundamental determinant of the properties of systems of electrons and nuclei. The minimum of V(r) along the internuclear axis between two bonded atoms is a natural and physically meaningful boundary point, at which the electrostatic forces of the two nuclei upon an element of charge exactly cancel. We propose that the distances from nuclei to V(r) bond minima provide the basis for a well-defined set of covalent radii. Density functional calculations at the B3PW91/6-311+G** level were carried out for 59 molecules to locate the V(r) minima in 95 bonds and use these as the basis for determining single- and multiple-bond covalent radii for eight first- and second-row atoms plus hydrogen. It was found to be unrealistic to assign a single covalent radius to each atom; different values are needed for bonds to first- and second-row atoms, as well as to hydrogen. Using these results, we are able to predict the bond lengths of 33 single and multiple bonds with average errors of less than 0.04 A relative to experimental data.

Journal Article↗