Intramolecular Polarization Research Articles

ABEEMσπ FLUCTUATING CHARGE FORCE FIELD APPLIED TO ALANINE DIPEPTIDE AND ALANINE DIPEPTIDE–WATER SYSTEMS

Atom-bond electronegativity equalization method at σπ level fused into molecular mechanics (ABEEMσπ/MM) divides the bond regions into σ and π bond regions on the basis of previous ABEEM/MM. It may suitably reflect intramolecular and intermolecular interaction and polarization. The fitting function k H-bond in the hydrogen bond (HB) interaction region increases the capability of ABEEMσπ/MM to simulate the hydration. Hydration of alanine dipeptide (AD) in aqueous solution is determined by the intramolecular and intermolecular HBs and the competition among the molecular packing effects. The acceptor molecule in HB complex contains at least one pair of lone pair electrons, sometimes contains π bonds, whose orientations directly effect the orientation of HBs. Therefore, ABEEMσπ/MM has obviously predominance to discuss the AD and AD–water systems, which contain many lone pair electrons, π bonds, and abundant HB nets. Properties of six AD conformers, clusters AD +( H2O )1–4 obtained from ABEEMσπ/MM agree well with the results of experiments, ab initio and other force fields. Structural and dynamical properties of the hydration water molecules have just embodied that the ABEEMσπ/MM gives correct hydration description relative to other force fields.

Differential Polarization of Spin and Charge Density in Substituted Phenoxy Radicals

We have carried out a theoretical study of a series of para-substituted phenoxy radicals in an effort to understand the factors influencing spin and charge density distribution in open-shell systems. The calculations reveal that the distribution of spin and charge are not correlated: cases were found for which spin and charge move together, whereas for other substituents the two quantities exhibit spatially distinct intramolecular polarizations. Charge density variations across the series were found to correlate well with both the Hammett (sigma(p)) and Hammett-Brown (sigma(p)+) constants for each substituent, indicating that inductive and/or resonance effects are primarily responsible for the polarization of charge within the molecule. In contrast, the distribution of unpaired spin density could not be adequately accounted for using any of the typical Hammett-type spin delocalization constants cited in the literature. We uncovered an empirical correlation between the polarization of spin density and the alpha-HOMO-alpha-LUMO gap of the substituted phenoxy radicals: this led to the development of a simple model based on a three-electron, two-orbital bonding scheme in which mixing between the HOMO of the substituent and the SOMO of the phenoxy moiety serves to define the nature and extent of unpaired spin polarization throughout the molecule. This analysis yielded a correlation coefficient of r > 0.97 for the 15 substituents examined in the study; spin polarization effects in compounds that exhibited the greatest deviation from this correlation could also be readily explained within the context of the model. The underlying reason for the ability to differentially polarize spin and charge likely stems from the fact that net unpaired spin density is completely carried by the unpaired electron (and thus tracks the spatial characteristics of the SOMO), whereas charge density reflects the behavior of all of the electrons of the system. These results could have implications in the field of molecular magnetism, suggesting a means for synthetically tuning the magnitude of intramolecular exchange interactions, as well as providing guidance for the design of catalysts for radical-radical coupling reactions.

X-Pol Potential: An Electronic Structure-Based Force Field for Molecular Dynamics Simulation of a Solvated Protein in Water.

A recently proposed electronic structure-based force field called the explicit polarization (X-Pol) potential is used to study many-body electronic polarization effects in a protein, in particular by carrying out a molecular dynamics (MD) simulation of bovine pancreatic trypsin inhibitor (BPTI) in water with periodic boundary conditions. The primary unit cell is cubic with dimensions ~54 × 54 × 54 Å(3), and the total number of atoms in this cell is 14281. An approximate electronic wave function, consisting of 29026 basis functions for the entire system, is variationally optimized to give the minimum Born-Oppenheimer energy at every MD step; this allows the efficient evaluation of the required analytic forces for the dynamics. Intramolecular and intermolecular polarization and intramolecular charge transfer effects are examined and are found to be significant; for example, 17 out of 58 backbone carbonyls differ from neutrality on average by more than 0.1 electron, and the average charge on the six alanines varies from -0.05 to +0.09. The instantaneous excess charges vary even more widely; the backbone carbonyls have standard deviations in their fluctuating net charges from 0.03 to 0.05, and more than half of the residues have excess charges whose standard deviation exceeds 0.05. We conclude that the new-generation X-Pol force field permits the inclusion of time-dependent quantum mechanical polarization and charge transfer effects in much larger systems than was previously possible.

Improvement of the NEMO potential by inclusion of intramolecular polarization

AbstractThe intermolecular electrostatic and induction energy of a NEMO potential which includes intramolecular polarization, are compared with a regular NEMO potential and a NEMO potential with configurationally dependent local properties. It is shown that the inclusion of intramolecular polarization improves the description of the intermolecular interactions when using the NEMO potential. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Stability, polarity, intramolecular interactions and π-electron delocalization for all eighteen tautomers rotamers of uracil. DFT studies in the gas phase

Complete tautomeric equilibria were investigated for uracil at the DFT(B3LYP)/6-311+G(d,p) level to establish the stability order of all possible 18 tautomers-rotamers in the gas phase and to characterize their internal effects, polarity and aromatic character. Although the di-NH form strongly predominates (100%) in the mixture, the NH–OH, di-OH and CH–NH forms can be also considered. The favored tautomer is moderately stabilized by intramolecular interactions (attractions of the NH and C=O groups); it is also moderately polar and moderately delocalized. Stability of the functional groups (both amide functions) seems to be more important than intramolecular interactions, polarity and aromaticity. This is probably the main factor that dictates the tautomeric preferences in the uracil molecule.

Beyond Point Charges: Dynamic Polarization from Neural Net Predicted Multipole Moments.

Intramolecular polarization is the change to the electron density of a given atom upon variation in the positions of the neighboring atoms. We express the electron density in terms of multipole moments. Using glycine and N-methylacetamide (NMA) as pilot systems, we show that neural networks can capture the change in electron density due to polarization. After training, modestly sized neural networks successfully predict the atomic multipole moments from the nuclear positions of all atoms in the molecule. Accurate electrostatic energies between two atoms can be then obtained via a multipole expansion, inclusive of polarization effects. As a result polarization is successfully modeled at short-range and without an explicit polarizability tensor. This approach puts charge transfer and multipolar polarization on a common footing. The polarization procedure is formulated within the context of quantum chemical topology (QCT). Nonbonded atom-atom interactions in glycine cover an energy range of 948 kJ mol(-1), with an average energy difference between true and predicted energy of 0.2 kJ mol(-1), the largest difference being just under 1 kJ mol(-1). Very similar energy differences are found for NMA, which spans a range of 281 kJ mol(-1). The current proof-of-concept enables the construction of a new protein force field that incorporates electron density fragments that dynamically respond to their fluctuating environment.

Intramolecular Charge Transfer Reaction, Polarity, and Dielectric Relaxation in AOT/Water/Heptane Reverse Micelles: Pool Size Dependence

Intramolecular charge transfer (ICT) reaction in a newly synthesized molecule, of 4-(1-morpholenyl) benzonitrile (M6C), in AOT/water/heptane reverse micelles at different pool sizes has been studied by using steady-state and time-resolved fluorescence emission spectroscopy. The pool size dependences of the reaction equilibrium constant and reaction rate have been explained in terms of the average polarity of the confined solvent pools estimated from the fluorescence emission Stokes shift of a nonreactive probe, coumarin 153, dissolved in these microemulsions. The complex permittivity measurements in the frequency range 0.01<or=nu/GHz<or=2 for these microemulsions at different pool sizes (0<or=w0<or=40) and AOT concentrations (0.1<or=c/M<or=0.5) at 298.15 K have also been performed. At sufficient water content, a large dispersion with a relaxation time of approximately 600 ps has been observed at approximately 300 MHz and attributed to the average reorientation of water molecules residing in the close vicinity of the polar interface of the AOT headgroup and n-heptane. The reorientation of these interfacial water molecules is probably responsible for the nanosecond component observed in numerous polar solvation dynamics experiments in these reverse micelles. Subsequently, the estimated polarity and the measured reorientational time scale have been used to explain the dramatic slowing down of the ICT reaction rate and its dependence on pool size in these confined environments.

Optimal Charge and Charge Response Determination through Conformational Space: Global Fitting Scheme for Representative Charge and Charge Response Kernel

We propose a global fitting scheme derived in the least-squares sense to estimate the optimal partial charge and charge response kernel (CRK), partial differential(Q(a))/partial differential(V(b)), with the data collected from conformational space sampling. We applied the global fitting method to the 1-butanol system and show the performance and accuracy of our global fitting procedure. In addition, we chose 1-pentanol as the test system for electronic structure change through conformational change and applied the global fitting method to it. From our study, it is indicated that intramolecular polarization can be influenced by intramolecular hydrogen bonding, and it is shown that our global fitting method can correspond to such a situation. Also, the global fitting procedure was tested on a large molecular system, 1-dodecanol. We show the results of the application of our fitting method for the system needed to sample large sets of data over a large conformational space. It is indicated that the nonlocality in intramolecular polarization in the alkyl chain sequence can be observed and that the large fluctuation of CRKs through nonbonded interactions such as intramolecular hydrogen bonding, as seen in the 1-pentanol case, can appear in common. The global fitting scheme we propose can be used for building molecular models considering polarization effects explicitly, even in the case of target systems that include many conformers.

Terahertz radiation from bacteriorhodopsin reveals correlated primary electron and proton transfer processes

The kinetics of electrogenic events associated with the different steps of the light-induced proton pump of bacteriorhodopsin is well studied in a wide range of time scales by direct electric methods. However, the investigation of the fundamental primary charge translocation phenomena taking place in the functional energy conversion process of this protein, and in other biomolecular assemblies using light energy, has remained experimentally unfeasible because of the lack of proper detection technique operating in the 0.1- to 20-THz region. Here, we show that extending the concept of the familiar Hertzian dipole emission into the extreme spatial and temporal range of intramolecular polarization processes provides an alternative way to study ultrafast electrogenic events on naturally ordered biological systems. Applying a relatively simple experimental arrangement based on this idea, we were able to observe light-induced coherent terahertz radiation from bacteriorhodopsin with femtosecond time resolution. The detected terahertz signal was analyzed by numerical simulation in the framework of different models for the elementary polarization processes. It was found that the principal component of the terahertz emission can be well described by excited-state intramolecular electron transfer within the retinal chromophore. An additional slower process is attributed to the earliest phase of the proton pump, probably occurring by the redistribution of a H bond near the retinal. The correlated electron and proton translocation supports the concept, assigning a functional role to the light-induced sudden polarization in retinal proteins.

An intramolecular induction correction model of the molecular dipole moment

A model for intramolecular polarization is presented. It is used to describe the changes in the molecular charge distribution occurring as a response to changes of dihedral angles in the molecule. The model is based on a multicenter multipole distribution of the molecular charge distribution. The electric field from this charge distribution induce dipole moments in the same molecule. The model contains atom type parameters to describe the damping of the electric field. A total of four atom types are used. The parameters are fitted to a calibration set with various functional groups, and tested against a validation set. The error obtained for the calibration set is reduced by 92% and by 88% for the validation set, if compared to an accurate state-of-the-art force field. It is shown that rotating the non-polarizable multicenter multipole distribution for the equilibrium geometry gives too large dipole moments for dihedral angles deviating from the equilibrium geometry. This will lead to too large long-range attractions in simulations. This problem is overcome by using the dipole polarizability correction suggested here, which gives dipole moments very close to the Hartree-Fock dipole moments obtained from reference calculations.

Magnetic Interactions in Supramolecular NO···HC⋮C Type Hydrogen-Bonded Nitronylnitroxide Radical Chains

Two paramagnetic building blocks, 2-(4-ethynyl-1-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (3) and 2-(5-ethynyl-2-pyridyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (4) were synthesized and crystallized. Single crystal X-ray studies of 3 and 4 show the formation of supramolecular head-to-tail one-dimensional H-bonded (N-O...H-C[triple bond]C- type) chain structures with O...C distances of 3.181 and 3.155 A, respectively. High-resolution isotropic liquid state (c<or=10(-4) M) electron spin resonance (ESR) spectroscopy studies of the well-isolated molecules confirmed the intramolecular spin polarization from the nitronylnitroxide radical group (acceptor, N-O) to the acetylenic proton (donor, H-C[triple bond]C-), which is mediated by the pi-conjugated backbone. The influence of the heteroatom (pyridine nitrogen-14N) in the ESR hyperfine splitting pattern was clearly seen in radical 4, with an additional number of lines appearing in the MI=0 line of the total five-line spectrum. The solution state paramagnetic 1H NMR investigation of radicals 2-(4-trimethylsilylethynyl-1-phenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (1) and 3 clearly support the intramolecular spin density propagation from the acceptor to the donor groups as well as the proton hyperfine coupling (hfc) values of the conjugated backbone determined by ESR studies. Bulk magnetic investigations of the polycrystalline chain compounds (3 and 4) in the temperature range 300 down to 4.5 K display antiferromagnetic exchange interactions at very low temperature. The experimental bulk magnetic data were found to be fit by using the dimer model with exchange coupling 2J/KB values of -3.10+/-1.16 and -8.00+/-3.83 K for 3 and 4, respectively, as well as by adopting the Heisenberg-chain model with 2J/KB values of -0.62+/-0.02 and -2.21+/-0.13 K for 3 and 4, respectively.

Force field modeling of conformational energies: Importance of multipole moments and intramolecular polarization

AbstractThe ability of force fields to reproduce relative conformational energies for seven molecules is probed. The correlation against LMP2/cc‐pVTZ results for standard force field employing fixed partial charges deteriorates as the molecules become more polar. Inclusion of multipole moments and intramolecular polarization can improve the correlation, and both contributions are of similar importance. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

Development, Validation, and Applications of Anisotropic Polarizable Molecular Mechanics to Study Ligand and Drug-Receptor Interactions

A correct representation of intermolecular interaction energies is necessary for reliable drug-receptor docking studies. While ab initio quantum chemistry with extended basis sets is the most accurate tool for that purpose, its use is precluded for very large molecular complexes. This constitutes the incentive for the development of accurate molecular mechanics potentials, in which the first-order electrostatic, and the second-order polarization energy contributions, are of essential importance. In this paper, we review the most important steps in the development of anisotropic, polarizable molecular mechanics (APMM) procedures. Among these, we illustrate validation tests of the ab initio-grounded, polarizable molecular mechanics potential, SIBFA (Sum of Interactions Between Fragments Ab initio computed). These are done by comparisons with parallel quantum-chemical (QC) results on representative multiply hydrogen-bonded complexes and polycoordinated complexes of one, or of two, divalent metal cations. For both kinds of complexes, the need to reproduce the non-additivity of the QC interaction energies is emphasized. One difficulty arises upon handling flexible molecules, due to the need to account simultaneously and consistently for the onset of inter- and intra-molecular polarization and charge-transfer effects. A new approach in the context of SIBFA was recently developed towards this aim, and tested in two cases of conformation-dependent cation-ligand interaction energies. The first relates to the complexes formed between the mecapto-carboxamide anion, an essential building-block of several Zn-metalloenzyme inhibitors, and Zn(II). The second relates to the complexes of the tetra-anionic pyrophosphate anion, a key building-block of ATP and GTP, with one or two divalent Zn(II) cations used as a probe. In the domain of applications, two recent studies are then presented. The first is the docking of the captopril drug to the active site of the binuclear Zn(II)- beta-lactamase enzyme. The second is the complex of a non-hydrolyzable analog of ATP with the active site of a binuclear Mg(II)-dependent kinase. An extension to an open-shell cation, Cu(II), is finally presented. The encouraging results presented in this review show that APMM procedures could be used in large-scale studies of ligand and drug-receptor interactions.

Site Affinity Effects upon Charge Injection into Siloxane-based Monolayers

Submolecular electrical information is successfully derived by applying element-specific, chemically resolved electrical measurements to a covalently bound stilbazole-based monolayer on a silicon substrate. Pronounced affinity effects are found in the response of adjacent atomic sites to external charge injection, accompanied by intramolecular polarization variations. These noncontact electrical read-out capabilities may provide a first entry toward the realization of organic devices based on submolecular electrical units.

Effects of HPE-101, a skin penetration enhancer, on human erythrocyte membranes

The primary aim of this study was to investigate the skin permeation-enhancing mechanism of HPE-101 using erythrocyte ghost cells prepared from human whole blood as a biomembrane model. The extent of hemolysis of erythrocytes induced by HPE-101 was measured using a spectrophotometer at 540 nm. The effect of HPE-101 on lipid fluidity was examined by observing the change of intramolecular excimer formation and fluorescence polarization using an intramolecular probe (1,3- bis(pyrene) propane) and a lipid probe (1,6-diphenyl 1,3,5-hexatriene), respectively. Hemolysis of erythrocytes was observed at 0.01 mM and completed at 1.0 mM of HPE-101. The fluorescence polarization of the ghost membrane decreased with the addition of HPE-101, whereas the intramolecular excimer formation increased. HPE-101 thus enhanced the rotational mobility and the lateral diffusion, thereby decreasing the microviscosity of ghost membranes, implying that HPE-101 increases the lipid fluidity of ghost membranes. Therefore, HPE-101 seems to cause an increase in fluidity of the lipid bilayers in the stratum corneum of the skin, resulting in the reduction of diffusion resistance.

Intramolecular polarization of the dative B [sbnd]O bond in the donor–acceptor complexes of 1-boraadamantanes with tetrahydrofuran

The X-ray diffraction studies and B3LYP/6-311G* calculations of the complexes of 1-boraadamantane and 4-bromo-1-boraadamantane with THF have revealed that the introduction of a halogen atom results in a shortening of the B–O bond due to intramolecular polarization.

Independent Calibration of 1H Spin-Diffusion Coefficients in Amorphous Polymers by Intramolecular Polarization Transfer

We report a general method, based on intramolecular spin diffusion, for the measurement and calculation of spin-diffusion coefficients in amorphous polymers and their blends using only NMR data. The basic structural unit that defines 1H polarization density in polymers is the monomer unit. Using appropriately selected internal reference distances calculated from energy-minimized chain dimension simulations, time scales for the redistribution of 1H polarization within amorphous homopolymers may be used to independently calculate maximum values of the spin-diffusion coefficients D. This strategy represents an attractive alternative to current methods employed for domain size measurements in polymer blends, which require calibration of spin-diffusion coefficients based on comparisons of similar NMR data obtained on model compounds analyzed previously using scattering or microscopy techniques. In this way, many more polymer systems become amenable to study by NMR spin-diffusion methods, since X-ray scattering...

Consistent treatment of inter- and intramolecular polarization in molecular mechanics calculations.

A protocol is described for the treatment of molecular polarization in force field calculations. The resulting model is consistent in that both inter- and intramolecular polarization are handled within a single scheme. An analytical formula for removing intramolecular polarization from a set of atomic multipoles for an arbitrary static structure or conformation is given. With the help of the intramolecular polarization, these permanent atomic multipoles can then be applied in modeling alternative conformations of a molecule. Equipped with this simple technique, one can derive transferable electrostatic parameters for peptides and proteins using flexible model compounds such as dipeptides. The proposed procedure is tested for its ability to describe the electrostatic potential around various configurations of the N-methylacetamide dimer. The effect of different intramolecular polarization schemes on the accuracy of a force field model of the electrostatic potential of alanine dipeptide is investigated. A group-based scheme for including direct intramolecular polarization is shown to be most successful in accounting for the conformational dependence of electrostatic potentials.

Intramolecular dynamic nuclear polarization via electron-nuclear double resonance

A fast and low power method is proposed and simulated for achieving substantial intramolecular dynamic nuclear polarization, as high as 50% for protons and 17% for deuterons, by means of simultaneous nuclear and allowed electronic magnetic resonance transitions.

Geometric separation of the polarization and charge transfer components of charge sensitivities of open molecular systems

The Hilbert space approach to the internal (isoelectronic) hardness and softness kernels is presented at the global and subsystem resolutions. A separation of components due to the intramolecular polarization (P) and external charge transfer (CT) is performed by projections into the complementary subspaces spanned by the P-vectors, eigenvectors of the molecular linear response operator, and the constant CT-vector. The quantities reflecting the P–CT coupling are discussed and explicit transformations between the (P, CT)-resolved perturbations and responses are reported.