QC calculation

The final part is devoted to a survey of molecular properties of special interest to the medicinal chemist. The Theory of Atoms in Molecules by R. F.W. Bader et al., presented in Chapter 7, enables the quantitative use of chemical concepts, for example those of the functional group in organic chemistry or molecular similarity in medicinal chemistry, for prediction and understanding of chemical processes. This contribution also discusses possible applications of the theory to QSAR. Another important property that can be derived by use of QC calculations is the molecular electrostatic potential. J.S. Murray and P. Politzer describe the use of this property for description of noncovalent interactions between ligand and receptor, and the design of new compounds with specific features (Chapter 8). In Chapter 9, H.D. and M. Holtje describe the use of QC methods to parameterize force-field parameters, and applications to a pharmacophore search of enzyme inhibitors. The authors also show the use of QC methods for investigation of charge-transfer complexes. 

We have adopted a strategy similar to that used in our development of polymer force fields in parameterization of an atomistic potential function for HMX. Specifically, we have undertaken a systematic investigation of conformational and intermolecular binding energies in model nitramine compounds (i.e., those containing the C2N-NO2 moiety ) using high-level QC calculations. In the case of HMX, a QC-based force field is the only realistic option due to insufficient spectroscopic data that would facilitate force field parameterization. 

Force field validation. In addition to ensuring that the force field reproduces results of QC calculations we have compared predictions of MD simulations using this force field with the available experimental data. Gas phase MD simulations using the quantum-chemistry based force field accurately reproduced the gas phase structure of DMNA as determined from electron diffraction studies. Liquid phase MD simulations of DMNA predicted the densities and solubility parameter as well as the activation energy and correlation times associated with molecular reorientation that are in good agreement with experimental data [34], As we will show in Section 4, comparison to structural and thermal data for the three pure crystalline polymorphs of HMX support the overall validity of our formulation and parameterization. 

In the following section of this paper we attempt to highlight these problems, and their possible solutions for some of the steps involved in QC calculations. 

Outline This review concentrates on work which mainly treats ILs from theoretical considerations and not from an experimental point of view. If calculations play only a supportive role in them, articles may have been neglected on principle. We also refrain from an introduction to methodological aspects and rather refer the reader to good textbooks on the subjects. The review is organized as follows Static QC calculations are discussed in detail in the next section including Hartree-Fock, density functional theory (Sect. 2.2) and correlated (i.e., more sophisticated) methods (Sect. 2.4) as well as semiempirical methods (Sect. 2.1). We start with these kinds of small system calculations because they can be considered as a basis for the other calculations, i.e., an insight into the intermolecular forces is obtained. 

Density functional theory is the most widely applied method in order to study small components of ILs such as ions or pairs by means of static QC calculations for reasons of low computational costs. In this part of the review we also include these articles that contain correlated methods such as second-order MP2 theory and coupled cluster calculations if the calculations are provided only for the purpose of comparison, but are not the main workhorse to obtain the data. 

According to a literature search, more than 140 papers on CyD modeling have been published in 2004 alone, in which QC calculations, [28, 29, 30], MM [31, 32,... 

Equation (13) is intended to describe the free energy barrier of a reactive site embedded in a polymer, where AR should correspond to the distance between the PPs in the experimental system where F is applied two polymers that are grafted onto a reactive site. Computational limitations prevent the use of model systems that accurately include polymers of sufficient length to ensure that (13) reliably reproduces experimental conditions. To overcome this limitation, Boulatov and coworkers employed the previously demonstrated relationship between the F applied along a conveniently defined local coordinate that applied between the PPs to cast (13) in a form amenable to use to quantities obtained through QC calculations of small model systems in the limit that G oo and R —> oo ... 

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