Purely descriptor

The consecuhve levels of 3D informahon are illustrated in Fig. 7.2. The pure cormechvity informahon is usually referred to as 2D. If stereo information is available, it can be referred to as 2.5D since the stereo descriptors add some 3D informahon. From this, a single 3D structure is obtained from the program GORINA [5] and, subsequently, a mulh-conformer ensemble from the program OMEGA [6] (bottom left). In this chapter, we will refer only to the step from 2D (2.5D) to 3D. 

A comparahve analysis of coefficients and descriptors clarifies the relationship between lipophilicity and hydrophobicity (Y in Eq. 4 is the molar volume which assesses the solute s capacity to elicit nonpolar interactions (i.e. hydrophobic forces) which, as also clearly stated in the International Union of Pure and Applied Chemistry definitions [3] are not synonyms but, when only neutral species are concerned, may be considered as interchangeable. In the majority of partitioning systems, the lipophilicity is chiefly due to the hydrophobicity, as is clearly indicated by the finding that the product of numerical values of the descriptors V and of the coefficient v is larger in absolute value than the corresponding product of other couples of descriptors/coefficients [9]. This explains the very common linear rela-... 

Korany et al. [28] used Fourier descriptors for the spectrophotometric identification of miconazole and 11 different benzenoid compounds. Fourier descriptor values computed from spectrophotometric measurements were used to compute a purity index. The Fourier descriptors calculated for a set of absorbencies are independent of concentration and is sensitive to the presence of interferents. Such condition was proven by calculating the Fourier descriptor for pure and degraded benzylpenicillin. Absorbance data were measured and recorded for miconazole and for all the 11 compounds. The calculated Fourier descriptor value for these compounds showed significant discrimination between them. Moreover, the reproducibility of the Fourier descriptors was tested by measurement over several successive days and the relative standard deviation obtained was less than 2%. 

In the multimedia models used in this series of volumes, an air-water partition coefficient KAW or Henry s law constant (H) is required and is calculated from the ratio of the pure substance vapor pressure and aqueous solubility. This method is widely used for hydrophobic chemicals but is inappropriate for water-miscible chemicals for which no solubility can be measured. Examples are the lower alcohols, acids, amines and ketones. There are reported calculated or pseudo-solubilities that have been derived from QSPR correlations with molecular descriptors for alcohols, aldehydes and amines (by Leahy 1986 Kamlet et al. 1987, 1988 and Nirmalakhandan and Speece 1988a,b). The obvious option is to input the H or KAW directly. If the chemical s activity coefficient y in water is known, then H can be estimated as vwyP[>where vw is the molar volume of water and Pf is the liquid vapor pressure. Since H can be regarded as P[IC[, where Cjs is the solubility, it is apparent that (l/vwy) is a pseudo-solubility. Correlations and measurements of y are available in the physical-chemical literature. For example, if y is 5.0, the pseudo-solubility is 11100 mol/m3 since the molar volume of water vw is 18 x 10-6 m3/mol or 18 cm3/mol. Chemicals with y less than about 20 are usually miscible in water. If the liquid vapor pressure in this case is 1000 Pa, H will be 1000/11100 or 0.090 Pa m3/mol and KAW will be H/RT or 3.6 x 10 5 at 25°C. Alternatively, if H or KAW is known, C[ can be calculated. It is possible to apply existing models to hydrophilic chemicals if this pseudo-solubility is calculated from the activity coefficient or from a known H (i.e., Cjs, P[/H or P[ or KAW RT). This approach is used here. In the fugacity model illustrations all pseudo-solubilities are so designated and should not be regarded as real, experimentally accessible quantities. 

The octanol-water partition coefficient, Kow, is the most widely used descriptor of hydrophobicity in quantitative structure activity relationships (QSAR), which are used to describe sorption to organic matter, soil, and sediments [15], bioaccumulation [104], and toxicity [105 107J. Octanol is an amphiphilic bulk solvent with a molar volume of 0.12 dm3 mol when saturated with water. In the octanol-water system, octanol contains 2.3 mol dm 3 of water (one molecule of water per four molecules of octanol) and water is saturated with 4.5 x 10-3 mol dm 3 octanol. Octanol is more suitable than any other solvent system (for) mimicking biological membranes and organic matter properties, because it contains an aliphatic alkyl chain for pure van der Waals interactions plus the alcohol group, which can act as a hydrogen donor and acceptor. 

A specific class of molecular descriptors is the one based on quantum chemical calculations. These descriptors may or may not be observables themselves. They may correspond to a computed value for some experimentally verifiable quantity, or they may be purely conceptual descriptors. A review of quantum chemical molecular descriptors has been given by Karelson et al. [9,10]. 

In many cases of practical interest, no theoretically based mathematical equations exist for the relationships between x and y we sometimes know but often only assume that relationships exist. Examples are for instance modeling of the boiling point or the toxicity of chemical compounds by variables derived from the chemical structure (molecular descriptors). Investigation of quantitative structure-property or structure-activity relationships (QSPR/QSAR) by this approach requires multivariate calibration methods. For such purely empirical models—often with many variables—the... 

A descriptor for an enzyme active site that permits binding of a family of related compounds (e.g., mimics of the reaction intermediate) that can be derived from the initial binding and conformational changes in the substrate. This concept arose from the observation that a number of monoterpene cyclases were incapable of discriminating between enantiomers of the reaction intermediate, even though the enzyme catalyzes the synthesis of an enantiomerically pure product from an achiral substrate. An example is trichodiene synthase which catalyzes the cyclization of farnesyl diphosphate to trichodiene. 

Calculated descriptors have generally fallen into two broad categories those that seek to model an experimentally determined or physical descriptor (such as ClogP or CpKJ and those that are purely mathematical [such as the Kier and Hall connectivity indices (4)]. Not surprisingly, the latter category has been heavily populated over the years, so much so that QSAR/QSPR practitioners have had to rely on model validation procedures (such as leave-k-out cross-validation) to avoid models built upon chance correlation. Of course, such procedures are far less critical when very few descriptors are used (such as with the Hansch, Leo, and Abraham descriptors) it can even be argued that they are unnecessary. 

For this task, easily accessible properties of mixtures or pure metabolites are compared with literature data. This may be the biological activity spectrum against a variety of test organisms. Widely used also is the comparison of UV [90] or MS data and HPLC retention times with appropriate reference data collections, a method which needs only minimal amounts and affords reliable results. Finally, there are databases where substructures, NMR or UV data and a variety of other molecular descriptors can be searched using computers [91]. The most comprehensive data collection of natural compounds is the Dictionary of Natural Products (DNP) [92], which compiles metabolites from all natural sources, also from plants. More appropriate for dereplication of microbial products, however, is our own data collection (AntiBase [93]) that allows rapid identification using combined structural features and spectroscopic data, tools that are not available in the DNP. 

Salinity measurements are most often used in oceanography to determine seawater density. The conventional measure used by oceanographers for determining salinity is conductivity. This is feasible because the salt content of seawater is well defined, as is the temperature-related compressibility. As an alternative, the refractive index of water is a good descriptor of density when temperature is known or can be measured. Refractive index provides a high-precision method for determining the density of pure water. As various salts are added, the refractive index is a less exact predictor of density, although relative measurements can still be useful. 

As chemists we can pose a simple, focussed question how do the Woodward-Hoffmann rules (WHR) [18] arise from a purely electron density formulation of chemistry The WHR for pericyclic reactions were expressed in terms of orbital symmetries particularly transparent is their expression in terms of the symmetries of frontier orbitals. Since the electron density function lacks the symmetry properties arising from nodes (it lacks phases), it appears at first sight to be incapable of accounting for the stereochemistry and allowedness of pericyclic reactions. In fact, however, Ayers et al. [19] have outlined how the WHR can be reformulated in terms of a mathematical function they call the dual descriptor , which encapsulates the fact that nucleophilic and electrophile regions of molecules are mutually friendly. They do concede that with DFT some processes are harder to describe than others and reassure us that Orbitals certainly have a role to play in the conceptual analysis of molecules . The wavefunction formulation of the WHR can be pictorial and simple, while DFT requires the definition of and calculations with some nonintuitive ( ) density function concepts. But we are still left uncertain whether the successes of wavefunctions arises from their physical reality (do they exist out there ) or whether this successes is merely because their mathematical form reflects an underlying reality - are they merely the shadows in Plato s cave [20]. 

Structural descriptors are implemented extensively in the development of prediction models for a large number of endpoints related to the fate and toxicity of organic chemicals in the environment and to human health. The TIs were reported for the modeling of properties of the pure substances such as boiling point (Basak et al., 1996), vapor pressure (Liang and Gallagher, 1998) and water... 

Inorganic chemicals (i.e., NaC03, K2S04) and pure chemical elements (i.e., Ni, P) are difficult to model and parameterize meaningful (or useful) descriptors for these chemicals may not be calculated from most computational chemistry programs. 

The stereo descriptor Z indicates that the configuration of both chirality centres in a molecule with only two chirality centres is the same. However, this does not give any information about the absolute configuration. Thus Z- 1,2-dichlorocyclobutane can mean a mixture of the enantiomers (R,R) and (S,S)-1,2-dichlorocyclobutane but can also be used for just one of the pure enantiomers. The priority order of the atoms attached to the chirality centres is Cl > C(C1,C,H) > C(C,H,H) > H. 

---