Rules on chiral and achiral molecular transformations

The properties of chiral and achiral transformations between mirror images ofn-dimensional point sets are investigated. Several rules are proven, relevant to chirality-preserving and chirality-abandoning molecular transformations.     

Rules on chiral and achiral molecular transformations. II

The properties of chiral and achiral transformations between mirror images of labeled, partially labeled and unlabeledn-dimensional point sets are investigated. Mislow's Label Paradox of three-dimensional chirality-preserving and chirality-abandoning molecular transformations of tetrahedra is generalized to simplexes of all higher dimensionsn, and a sufficient and necessary partial labeling condition is given for fully chiral interconversion paths of mirror images of chiraln-dimensional simplexes.     

Alternative chiral thiols for preparation of chiral CdS quantum dots covered immediately by achiral thiols

Developing of alternative chiral thiol stabilizers from the assembly of achiral thiol (e.g. thioglycolic acid) and chiral ligand (e.g. arginine) via both hydrogen bonding and electrostatic interactions was proposed and successfully applied to an efficient preparation of chiral CdS quantum dots (QDs). Chiral CdS QDs capped mainly with achiral thioglycolic acid were also obtained that may allow the chiral QDs to be modified for extended applications.     

Single switch surface hopping for molecular quantum dynamics

The aim of this text is to present a surface hopping approximation for molecular quantum dynamics obeying a Schr?dinger equation with crossing eigenvalue surfaces. After motivating Schr?dinger equations with matrix valued potentials, we describe the single switch algorithm and present some numerical results. Then we discuss the algorithm’s mathematical justification and describe extensions to more general situations, where three eigenvalue surfaces intersect or the eigenvalues are of multiplicity two. We emphasize the generality of this surface hopping approximation for non-adiabatic transitions.     

The dynamo library for molecular simulations using hybrid quantum mechanical and molecular mechanical potentials

The Dynamo module library has been developed for the simulation of molecular systems using hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials. Dynamo is not a program package but is a library of Fortran 90 modules that can be employed by those interested in writing their own programs for performing molecular simulations. The library supports a range of different types of molecular calculation including geometry optimizations, reaction‐path determinations and molecular dynamics and Monte Carlo simulations. This article outlines the general structure and capabilities of the library and describes in detail Dynamo's semiempirical QM/MM hybrid potential. Results are presented to indicate three particular aspects of this implementation—the handling of long‐range nonbonding interactions, the nature of the boundary between the quantum mechanical and molecular mechanical atoms and how to perform path‐integral hybrid‐potential molecular dynamics simulations. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 1088–1100, 2000     

Phase coherent electronics: a molecular switch based on quantum interference

The phenomenon of quantum mechanical interference may be used to control the conductivity of ballistic molecular wires. Using a simple model we demonstrate plausible effects and discuss its potential uses for constructing coherence-based molecular electronics.     

Conformational flexibility in open chain molecules: chiral and achiral alkanes

Conformational partition functions of chiral and achiral alkanes have been computed by using a continuum approach (instead of rotational isomeric state approximations). The accessible conformational space per bond depends upon the structure of the compound and is only in the range of 5–13% of the maximum accessible range. In order to partly overcome the intrinsic ambiguity of the term “conformational flexibility”, the distinction between number flexibility (a measure of the number of accessible energy minima) and space flexibility (a measure of the total allotted space) is proposed. Further, the conformational versatility of each bond of a molecule is evaluated in terms of the a priori probability density function of that bond, and it is shown that the use of this function permits a comparison of the relative conformational flexibilities of the individual bonds, which is particularly useful for molecules having more than two rotation angles (where the conventional energy maps cannot be used). Optical rotations are calculated for a series of chiral alkanes by combining the continuum approach for conformational analysis and a recent optical activity calculation scheme. Contributions of single bonds to the molar optical rotation are evaluated and discussed. The influence of temperature upon conformational and chiral properties is evaluated.     

Simulated scaling method for localized enhanced sampling and simultaneous "alchemical" free energy simulations: a general method for molecular mechanical, quantum mechanical, and quantum mechanical/molecular mechanical simulations

A potential scaling version of simulated tempering is presented to efficiently sample configuration space in a localized region. The present "simulated scaling" method is developed with a Wang-Landau type of updating scheme in order to quickly flatten the distributions in the scaling parameter lambdam space. This proposal is meaningful for a broad range of biophysical problems, in which localized sampling is required. Besides its superior capability and robustness in localized conformational sampling, this simulated scaling method can also naturally lead to efficient "alchemical" free energy predictions when dual-topology alchemical hybrid potential is applied; thereby simultaneously, both of the chemically and conformationally distinct portions of two end point chemical states can be efficiently sampled. As demonstrated in this work, the present method is also feasible for the quantum mechanical and quantum mechanical/molecular mechanical simulations.     

Trajectory-based solution of the nonadiabatic quantum dynamics equations: an on-the-fly approach for molecular dynamics simulations

The non-relativistic quantum dynamics of nuclei and electrons is solved within the framework of quantum hydrodynamics using the adiabatic representation of the electronic states. An on-the-fly trajectory-based nonadiabatic molecular dynamics algorithm is derived, which is also able to capture nuclear quantum effects that are missing in the traditional trajectory surface hopping approach based on the independent trajectory approximation. The use of correlated trajectories produces quantum dynamics, which is in principle exact and computationally very efficient. The method is first tested on a series of model potentials and then applied to study the molecular collision of H with H(2) using on-the-fly TDDFT potential energy surfaces and nonadiabatic coupling vectors.     

Pyridine-containing chiral macrocycles for the enantioselective recognition of amino acid derivatives and their molecular dynamics simulations

Two novel C₂-symmetric optically active pyridine-15-crown-5 type ligands containing lipophilic chains at the stereogenic centres, macrocycles 5 and 6, were prepared from (S)-1,2-propanediol and (S)-3-aryloxy-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives. These novel macrocycles have been shown to be strong complexing agents for primary organic ammonium salts (with K values of up to 1363.5 M^?1, ΔG^o of up to 17.86 kJ mol^?1 and a selectivity ratio of 80:20) by ¹H NMR titration method. These macrocyclic host exhibited enantioselective binding towards the l-enantiomer of phenylalanine methyl ester hydrochloride with K_L/K_D up to 8.57 in CDCl₃ containing 0.25% CD₃OD. Experimental results have been detailed with molecular dynamic calculations at atomic level concerning the molecular recognition and discrimination properties of a chiral pyridino-15-crown-5. The binding free energies were calculated as ～?25 kJ mol^?1. The results indicated that the host binds and discriminates valine salts better than phenylalanine salts. The molecular dynamics, MM/PBSA calculations are consistent with the ¹H NMR results.     

Finite element interpolation for combined classical/quantum mechanical molecular dynamics simulations

A method is presented to interpolate the potential energy function for a part of a system consisting of a few degrees of freedom, such as a molecule in solution. The method is based on a modified finite element (FE) interpolation scheme. The aim is to save computer time when expensive methods such as quantum-chemical calculations are used to determine the potential energy function. The expensive calculations are only carried out if the molecule explores new unknown regions of the conformation space. If the molecule resides in regions previously explored, a cheap interpolation is performed instead of an expensive calculation, using known neighboring points. We report the interpolation techniques for the energies and the forces of the molecule, the handling of the FE mesh, and an application to a simple test example in molecular dynamics (MD) simulations. Good performance of the method was obtained (especially for MD simulations with a preceding Monte Carlo mesh generation) without losing accuracy. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1484–1495, 1997     

A molecular dynamics study of chirality transfer: The impact of a chiral solute on an achiral solvent

A solvation shell may adapt to the presence of a chiral solute by becoming chiral. The extent of this chirality transfer and its dependence on the solute and solvent characteristics are explored in this article. Molecular dynamics simulations of solvated chiral analytes form the basis of the analysis. The chirality induced in the solvent is assessed based on a series of related chirality indexes originally proposed by Osipov [M. A. Osipov et al., Mol. Phys. 84, 1193 (1995)]. Two solvents are considered: Ethanol and benzyl alcohol. Ethanol provides insight into chirality transfer when the solvent interacts with the solute primarily by a hydrogen bond. Several ethanol models have been considered starting with a nonpolarizable model, progressing to a fluctuating charge model, and finally, to a fully polarizable model. This progression provides some insights into the importance of solvent polarizability in the transfer of chirality. Benzyl alcohol, by virtue of the aromatic ring, increases the number of potential solvent-solute interactions. Thus, with these two solvents, the issue of compatibility between the solvent and solute is also considered. The solvation of three chiral solutes is examined: Styrene oxide, acenaphthenol, and n-(1-(4-bromophenyl)ethyl)pivalamide (PAMD). All three solutes have the possibility of hydrogen bonding with the solvent, the last two may also form ring-ring interactions, and the last also has multiple hydrogen bonding sites. For PAMD, the impact of conformational averaging is examined by comparing the chirality transfer about rigid and flexible solutes.     

Template effect in the competition between Haeckelite and graphene growth on Ni(111): quantum chemical molecular dynamics simulations

Quantum chemical molecular dynamics (QM/MD) simulations of ensembles of C(2) molecules on the Ni(111) terrace show that, in the absence of a hexagonal template or step edge, Haeckelite is preferentially nucleated over graphene as a metastable intermediate. The nucleation process is dominated by the swift transition of long carbon chains toward a fully connected sp(2) carbon network. Starting from a pentagon as nucleus, pentagons and heptagons condense during ring collapse reactions, which results in zero overall curvature. To the contrary, in the presence of a coronene-like C(24) template, hexagonal ring formation is clearly promoted, in agreement with recent suggestions from experiments. In the absence of step edges or molecular templates, graphene nucleation follows Ostwald's "rule of stages" cascade of metastable states, from linear carbon chains, via Haeckelite islands that finally anneal to graphene.     

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

Molecular dynamics (MD) simulations were used to investigate the binding of six chiral compounds to the amino acid-based molecular micelle (MM) poly-(sodium undecyl-(L)-leucine-leucine) or poly(SULL). The MM investigated is used as a chiral selector in capillary electrophoresis. The project goal was to characterize the chiral recognition mechanism in these separations and to move toward predictive models to identify the best amino acid-based MM for a given separation. Poly(SULL) was found to contain six binding sites into which chiral compounds could insert. Four sites had similar sizes, shapes, and electrostatic properties. Enantiomers of alprenolol, propranolol, 1,1′-bi-2-naphthyl-2,2′-diyl hydrogen phosphate, 1,1′-bi-2-naphthol, chlorthalidone, or lorazepam were separately docked into each binding pocket and MD simulations with the resulting intermolecular complexes were performed. Solvent-accessible surface area calculations showed the compounds preferentially associated with binding sites where they penetrated into the MM core and shielded their non-polar atoms from solvent. Furthermore, with five of the six compounds the enantiomer with the most favorable free energy of MM association also experienced the most favorable intermolecular hydrogen bonding interactions with the MM. This result suggests that stereoselective intermolecular hydrogen bonds play an important role in chiral discrimination in separations using amino acid-based MMs.GRAPHICAL ABSTRACT     

Expression of molecular chirality and two-dimensional supramolecular self-assembly of chiral, racemic, and achiral monodendrons at the liquid-solid interface

We have investigated the two-dimensional ordering of chiral and achiral monodendrons at the liquid-solid interface. The chiral molecules self-assemble into extended arrays of dimers. As expected, the R enantiomer forms the mirror image type pattern of the chiral two-dimensional structure formed by the S enantiomer. A racemic mixture applied from solution onto the substrate undergoes spontaneous segregation: the enantiomers separate on the surface and appear in different domains. In contrast to the chiral molecules, the achiral analogue self-assembles into cyclic tetramers. Moreover, the pattern formed by the achiral molecule strongly depends on the solvent used. In the case of 1-phenyloctane, solvent molecules are coadsorbed in a 2:1 (dendron:solvent) ratio whereas in 1-octanol, no solvent molecules are coadsorbed. By the appropriate solvent choice, the distance between the potential "supramolecular containers" can be influenced.     

Conformational properties of penicillins: quantum chemical calculations and molecular dynamics simulations of benzylpenicillin

Herein, we present theoretical results on the conformational properties of benzylpenicillin, which are characterized by means of quantum chemical calculations (MP2/6-31G* and B3LYP/6-31G*) and classical molecular dynamics simulations (5 ns) both in the gas phase and in aqueous solution. In the gas phase, the benzylpenicillin conformer in which the thiazolidine ring has the carboxylate group oriented axially is the most favored one. Both intramolecular CH. O and dispersion interactions contribute to stabilize the axial conformer with respect to the equatorial one. In aqueous solution, a molecular dynamics simulation predicts a relative population of the axial:equatorial conformers of 0.70:0.30 in consonance with NMR experimental data. Overall, the quantum chemical calculations as well as the simulations give insight into substituent effects, the conformational dynamics of benzylpenicillin, the frequency of ring-puckering motions, and the correlation of side chain and ring-puckering motions.     

Rational optimization of the Whelk-O1 chiral stationary phase using molecular dynamics simulations

Rational in silico optimization of the Whelk-O1 chiral stationary phase (CSP) has been carried out based on the chiral recognition mechanism extracted from previous molecular dynamics simulations [C.F. Zhao, N.M. Cann, Anal. Chem. 80 (2008) 2426] of this CSP. Three modified CSPs have been examined. The first two are designed to increase selectivity by reducing the docking probability of the less retained analyte. The third modified selector reverses the amide bridge to introduce a structural motif found in the popular carbamate-derivatized polysaccharide CSPs [Y. Okamoto, M. Kawashima, K. Hatada, J. Am. Chem. Soc. 106 (1984) 5357]. For each modified selector, an atomistic model has been obtained through extensive ab initio calculations. The effect of selector modification is then evaluated via simulations of the modified interface in the presence of target analytes. Simulation results show that the separation factors are increased for the modified CSPs but in some cases elution orders are reversed. The Whelk-O1 CSP was originally designed to separate naproxen [W.H. Pirkle, C.J. Welch, B. LAmm, J. Org. Chem. 57 (1992) 3854]. With this in mind, molecular dynamics simulations of naproxen are compared for the original, and the modified, selectors.     

Binding of cationic and neutral phenanthridine intercalators to a DNA oligomer is controlled by dispersion energy: quantum chemical calculations and molecular mechanics simulations

Correlated ab initio as well as semiempirical quantum chemical calculations and molecular dynamics simulations were used to study the intercalation of cationic ethidium, cationic 5-ethyl-6-phenylphenanthridinium and uncharged 3,8-diamino-6-phenylphenanthridine to DNA. The stabilization energy of the cationic intercalators is considerably larger than that of the uncharged one. The dominant energy contribution with all intercalators is represented by dispersion energy. In the case of the cationic intercalators, the electrostatic and charge-transfer terms are also important. The DeltaG of ethidium intercalation to DNA was estimated at -4.5 kcal mol(-1) and this value agrees well with the experimental result. Of six contributions to the final free energy, the interaction energy value is crucial. The intercalation process is governed by the non-covalent stacking (including charge-transfer) interaction while the hydrogen bonding between the ethidium amino groups and the DNA backbone is less important. This is confirmed by the evaluation of the interaction energy as well as by the calculation of the free energy change. The intercalation affects the macroscopic properties of DNA in terms of its flexibility. This explains the easier entry of another intercalator molecule in the vicinity of an existing intercalation site.