Quantitative descriptors

In chemoinformatics, chirality is taken into account by many structural representation schemes, in order that a specific enantiomer can be imambiguously specified. A challenging task is the automatic detection of chirality in a molecular structure, which was solved for the case of chiral atoms, but not for chirality arising from other stereogenic units. Beyond labeling, quantitative descriptors of molecular chirahty are required for the prediction of chiral properties such as biological activity or enantioselectivity in chemical reactions) from the molecular structure. These descriptors, and how chemoinformatics can be used to automatically detect, specify, and represent molecular chirality, are described in more detail in Chapter 8. 

It is important to note that and C2 are quantitative descriptors of the gel effect which depend only on the monomer, temperature and reaction medium. The full description of given by equation (11), requires g and g2 which are functions of the rate of initiation and extent of conversion. The kinetic parameters used in these calculations and their sources are given in Table 1. All data are in units of litres, moles and second. Figure 5 shows the temperature dependencies of and C2 and Table 2 lists these and other parameters determined by fitting the model to the data in Figures 1-4. 

The quantitative descriptor of lipophilicity, the partition coefficient P, is defined as the ratio of the concentrations of a neutral compound in organic and aqueous phases of a two-compartment system under equilibrium conditions. It is commonly used in its logarithmic form, logP. Whereas 1-octanol serves as the standard organic phase for experimental determination, other solvents are applied to better mimic special permeation conditions such as the cyclohexane-water system for BBB permeation. Measurement of log P is described in Chapters 12 and 13 as well as in Ref [22]. 

Three-dimensional (3-D) descriptors of molecules quantify their shape, size, and other structural characteristics which arise out of the 3-D disposition and orientation of atoms and functional groups of molecules in space. A special class of 3-D indices is quantitative descriptors of chirality. If a molecule has one or more chiral centers, the spatial disposition of atoms can produce enantiomers, many of which will have the same magnitude of calculated and experimental physicochemical properties having, at the same time, distinct bioactivity profiles. Basak and coworkers [22] have developed quantitative chirality indices to discriminate such isomers according to their structural invariants which are based on the Cahn-Ingold-Prelog (CIP) rules. 

The stability of oxygen-centered radicals has been studied repeatedly in recent years in search of quantitative descriptors of antioxidant activity. The antioxidant activity of phenols is indeed so well correlated with O - H BDEs and the ionization potential that these two energies can be used as the guiding... 

The constant c represents the effect of change in applied pressure on the compact porosity. The authors examined several pharmaceutical powders (Acetaminophen, Emcompress or DCP, lactose, MCC, and com starch) to estimate the value of c and determine if it is a true representation of the compressibility of a given material (Fig. 10) (94). It was found that the parameter, c, provides a good representation of material compressibility for single- and multi-component systems. Thus, the relationship promises to be a useful quantitative descriptor of deformation behavior of pharmaceutical powders (94). 

However, potentially affected citizens may look at these quantitative descriptors as only partially describing the risk. They may consider a number of other factors such as the voluntariness, catastrophic potential, familiarity, and controllability of the hazard. Thus, contrary to the scientist, they may consider the one in a million risk to be more serious than the one in a thousand risk. Government officials are often reminded of this at public meetings, when people who smoke express great concern about very low levels of environmental contaminants which pose much lower health risks than smoking. 

Theoretical (computational) calculations can also offer quantitative descriptors of physicochemical properties of the molecular structures, molecular interactions, and thermodynamics of interactions. Principally, extensive studies on the catalytic site of GP have been exploited in theoretical QSAR studies [4]. The techniques engaged correlate biochemical behaviors with the known crystallographic structures, and map regions around the inhibitor molecule and added water molecules to improve the in silico prediction [106-110]. 

The Q is put into QSAR by describing the structure of a compound in a quantitative way, the simplest examples of quantitative descriptors being the mass of the compound or the number of atoms present. When the compound is described using physical, as opposed to structural, properties the relationship becomes a PAR. Correlations of this type have been used in the perfumery industry to describe and predict the substantivity and retention of fragrance ingredients that is, the ability of a compound to stick to and remain bound to surfaces such as hair, skin or cloth (see Chapter 11 for more details). 

This situation also holds in assigning quantitative descriptors to polymeric repeat units for the purpose of predicting certain locally anisotropic physical properties. Some locally anisotropic properties of polymers are more sensitive to the total number NBB of atoms on the... 

When the problem or risk issue is well understood an appropriate tool for risk analysis has to be chosen. For the hazards identified during the brainstorm the associated risks has to be estimated. This may be a qualitative description eventually using semi-quantitative descriptors, as high , medium or low or it may be a quantitative analysis with scores according to a pre-defined scale. The estimation of risks in Sect. 21.3 occurred following a qualitative method. It enabled the prioritisation of two risks within a rather simple process and no comparison to a fixed value was felt to be necessary. 

Enthalpy is the prime quantitative descriptor of chemical energetic stability enthalpy variations reflect the energetic gain cashed in, or the energetic price paid, when the nuclei and electrons of a chemical system break apart from one structure and coalesce into another structure. Enthalpy differences can be measured by calorimetric experiments, either directly or through specific heat measurements, or calculated by... 

Table 1.2 presents atomic non-bonding radii obtained by surveys of atom-atom contacts in organic crystal structures [8-11]. What are these numbers They are precisely what has just been said one half of the statistically most frequent distance between pairs of atoms of each atomic species in crystals. What can they be used for As Kitaigorodski proposed many years ago [8], the outer boundary of the molecule is the envelope surface of these overlapping spheres. In this way, a model of the molecule can be built that gives an immediate impression of space occupation, because neighbor molecules may come into close contact only to an extent that does not involve a large intermolecular overlap of the molecular envelopes. An additional bonus of this model is that molecular volume and the area of a molecular surface can be easily and accurately calculated (see below). These numbers are quantitative descriptors of the space size of a molecule. 

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