Formulae descriptors

Molecules are usually represented as 2D formulas or 3D molecular models. WhOe the 3D coordinates of atoms in a molecule are sufficient to describe the spatial arrangement of atoms, they exhibit two major disadvantages as molecular descriptors they depend on the size of a molecule and they do not describe additional properties (e.g., atomic properties). The first feature is most important for computational analysis of data. Even a simple statistical function, e.g., a correlation, requires the information to be represented in equally sized vectors of a fixed dimension. The solution to this problem is a mathematical transformation of the Cartesian coordinates of a molecule into a vector of fixed length. The second point can... 

In the Fischer convention, the ermfigurations of other molecules are described by the descriptors d and L, which are assigned comparison with the reference molecule glyceraldehyde. In ertqrloying the Fischer convention, it is convenient to use projection formulas. These are planar representations defined in such a w as to convey three-dimensional structural information. The molecule is oriented with the major carbon chain aligned vertically in such a marmer that the most oxidized terminal carbon is at the top. The vertical bonds at each carbon are directed back, away fiom the viewer, and the horizontal bonds are directed toward the viewer. The D and L forms of glyceraldehyde are shown below with the equivalent Fischer projection formulas. 

Scheme 9. The threo 2,3-diol problem. The erythro/threo notation is based on Fischer projection formulas. For example, if threo 2,3-diol 28, shown here in a staggered zigzag conformation, was depicted in an eclipsed Fischer projection, the adjacent hydroxyls attached to carbons 2 and 3 would reside on opposite sides of the carbon chain. An alternative, perhaps less ambiguous, descriptor is the syn/anti notation.63...

Most of the models and descriptors discussed so far are based on the two-dimensional representation of the compounds, i.e. on their structural formula. 

Commonly used molecular descriptor types are listed. For each category, one or two representative examples are given. Dimensionality refers to the molecular representation (molecular formula, 2D drawing, or 3D conformation) from which the descriptors are calculated (adapted from ref. 4). 

When molecules are represented by high-dimensional descriptors such as 2D fingerprints or several hundred topological indices, then the diversity of a library of compounds is usually calculated using a function based on the pairwise (dis)similarities of the molecules. Pairwise similarity can be quantified using a similarity or distance coefficient. The Tanimoto coefficient is most often used with binary fingerprints and is given by the formula below ... 

More complex devices have been developed that are capable of dealing with all cases. The reader is referred to the Nomenclature of Inorganic Chemistry, Chapter 10. The use of stereochemical descriptors in organic names and formulae is dealt with in Chapter 3, Section 3.8 (p. 21). 

The use of stereochemical descriptors in both names and formulae is dealt with in Chapter 3, Section 3.8 (p. 21). 

C-3 of 1 is correctly specified by Mislow and Siege] as r, C-3 of both 2 and ent-2 are incorrectly specified as R. If this were the CIP specification then the system would indeed have to be criticized but the system 3 4 (see Section 1.1.5.3.2.) gives precedence to stereogenicity over local symmetry in fact, it demands a reflection-invariant descriptor, i.e., r, as stated in the formulas. 

Masamune s descriptors syn and anti, appealing because of their conformity with modern customs of writing formulas, are currently widely in use. But, assuming they are used according to definition, they suffer from exactly the same fundamental limitations as c-erythrojc-threo or any other soft descriptor. Unfortunately, Masamune did not exhaust the area of an unambiguous soft description by restricting the simply defined models to C-C(HX)-C(HY)-C rather than C —C(XY) —C(XZ) —C (see Table 10). 

Additional soft or hard , i.e., CIP based, rules are required. Usually today, the latter course is taken, with the result that the initial inconvenience is reintroduced and all the disadvantages of soft and hard descriptions are combined. The consequence is obvious if the deviation is made from the clearly defined operating area of a soft description, then it is better to only give a formula which unambiguously describes relative configuration and leave it to the experts of CAS, Beilstein etc. to specify the example by proper descriptors. 

Attempts to produce descriptors similar to cis and trims for stereochemicidly more complicated coordination entities have tailed to achieve generality, and labels such as foe and mer are no longer recommended. Nevertheless, a diastereoisomeric structure may be indicated for any polyhedron using a configuration index as an affix to the name or formula. Finally, the chiralities of enantiomeric structures can be indicated using chirality symbols. 

Nowadays, more than 4000 types of descriptors are known.17 There exist different ways to classify them. With respect to the type of molecular representation used for their calculations—chemical formula, molecular graph, or spatial positions of atoms—one speaks about ID, 2D, and 3D descriptors, respectively. Descriptors can be global (describing the molecule as a whole) and local (only selected parts are considered). One could distinguish information-based descriptors, which tend to code the information stored in molecular structures, and knowledge-based (or semiempir-ical) descriptors issued from the consideration of the mechanism of action. Most of those descriptors can be obtained with the DRAGON, CODESSA PRO, and ISIDA programs. 

Although the term vitamin A has been used to denote specific chemical compounds, such as retinol or its esters, this term now is used more as a generic descriptor for compounds that exhibit the biological properties of retinol. Retinoid refers to the chemical entity retinol or other closely related naturally occurring derivatives. Retinoids also include structurally related synthetic analogues, which need not have retinol-like (vitamin A) activity. The structural formulas for the vitamin A family of retinoids are shown in Figure 66.3. Retinol (vitamin Aj), a primary alcohol, is present in esterihed form in the tissues of animals and saltwater fish, mainly in the liver. A closely related compound, 3-dehydroretinol (vitamin A2), is obtained from the tissues of freshwater fish and usually occurs mixed with retinol. 

Cons Data quality for HT synthesis and testing (reproducibility, homogeneity, scale-up ability), as shown for this case of metals/mixed oxides WGS and Selox catalysts, remains a drawback for efficient data-mining. As such, even if the trends for new catalytic formulas may still be detected, even in the presence of poorly reproducible systems or outliers, the ultimate target of predicting the quantitative performance of a catalyst after teaching an ANN with experimental data was found to require new catalysts descriptors that would contain more information than the simple elemental composition of the materials. 

Full details of the QSAR training set should be provided, including details of chemical structure (names and structural formulae, and chemical abstract service [CAS] numbers if available) and, in the case of a QSAR, data for all descriptor and response variables. If the data used to develop the model were based upon the processing of raw data (e.g., the averaging of replicate values), it is preferable if all of the raw data are supplied. 

Are the two faces of the double bonds in the compounds represented by the following formulae homotopic, enantiotopic or diastereotopic Give, where appropriate, a suitable descriptor for the face oriented towards you. 

Identify the stereogenic units in the molecules represented by the following formulae, assign appropriate stereo descriptors and indicate what type of isomerism is possible in these compounds. 

The structural formula of this new cytostatic (picoplatin) is shown below. In determining the stereo descriptor, the situation arises here that the highest ranking ligand occurs twice. In such cases the priority number of the ligand coordinated trans to it with the lowest priority (i.e. with the highest priority number) is used as the configuration index (principle of trans maximum difference). 

Any type of selected descriptor will provide a more or less complex characterization of each virtual library component. The use of similarity indices offers a straightforward method to evaluate similarities between virtual compounds. These indices use a bit-string representation for any descriptor (distances, fingerprints, pharmacophores, and so on) and, by simply counting the presence or the absence of specific bins and comparing the bit strings of virtual compounds, provide a numerical similarity index. The formula for the commonly used Tanimoto similarity index (71, 43), which can readily be transformed into the complementary diversity index, is reported in Fig. 5.14... 

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