Diversity voids

In the initial phase of compound selection, the strategy was to select compounds that filled diversity voids . Diversity voids are defined as regions of a chemistry space that are not populated with compounds from the PRCC. It should be noted, however, that regions of chemistry space might not be populated by molecules of interest in drug design or, for that matter, by molecules of any type since chemistry space is, in general, sparse. 

DVS offers a cell-based method for assessing the diversity of compound collections. The orthogonal chemistry space is partitioned into cells, and the occupancy of each cell is easily determined. Diversity voids , or unoccupied regions of chemistry space, are identified with unoccupied cells or cells of low occupancy, which are also easily recognized. Enhancing diversity of a compound collection thus consists of filling empty and low-occupancy cells (see Figure 13.5). 

An advantage of cell-based methods is that they allow the explicit identification of those regions of the chemical space that are underrepresented, or, even unrepresented (i.e., diversity voids), in a database thus suggesting alternative potential structures to those of the existing chemicals [Pearlman and Smith, 1998]. 

As mentioned above, corporate chemical structure databases are replete with analog series and are thus far from representative of the full range of structural or physicochemical diversity. There is therefore much interest in, first, locating the diversity voids within a particular collection, and then analyzing external collections to see which compounds could be purchased to occupy those holes. In this way, the molecular diversity of a corporate collection can be enhanced, and this in turn should lead to better results from high-... 

Select the initial set of vendor compounds by filling diversity voids... 

Fig. 1.18 Schematic depiction of a model 2-D eell-based selection process for compound acquisition (Cf [162]). In a unfllkdcircles represent eompounds in the original eompound DB in h filled circles represent compounds in the combined, pre-proeessed vendor DB c depicts the augmented compound DB after the initial selection process has been completed. Cells shaded in light grey represent diversity voids for cells eontaining fewer than two compounds. (See text for addition details)...

An alternative approach to that described above has been described by Lajiness [63]. It is a variant of the MaxD ( Dfragall ) algorithm preserrted earlier and is summarized in Table 1.8. One clear deficiency of this algorithm is that it is difficult to fill specific diversity voids. 

A mixture of PhenoHc MicrobaUoons and resin binder has a putty-like consistency. It can be molded to shape, troweUed onto surfaces, or pressed into a core. Curing gives a high strength, low density (0.144 g/cm ) foam free of voids and dense areas, and without a brittle skin. Syntactic foams are used in widely diverse appHcations, including boat flotation aids stmctural parts in aircraft, submarines, and missiles stmctural cores for waU panels and ablative heat shields for reentry vehicles and rocket test engines. 

Elemental boron is used in very diverse industries from metallurgy (qv) to electronics. Other areas of appHcation include ceramics (qv), propulsion, pyrotechnics, and nuclear chemistry. Boron is nontoxic. Workplace hygienic practices, however, include a voiding the breathing of boron dust or fine powder. 

In this work positron annihilation lifetime spectroscopy (PALS) was used to investigate structural diversity inside zeolite precursor matrix caused by the presence of alkali cations Na, K, Rb and Cs. PALS is an established and well-proven method for structural investigations of various materials, extensively used for metals and alloys, semiconductors and porous materials [3, 4]. In the investigations of zeolites PALS has been mostly used for their void structure and size study [5, 6, 7, 8], also in correlation to... 

Dissimilarity and clustering methods only describe the compounds that are in the input set voids in diversity space are not obvious, and if compounds are added then the set must be re-analyzed. Cell-based partitioning methods address these problems by dividing descriptor space into cells, and then populating those cells with compounds [67, 68]. The library is chosen to contain representatives from each cell. The use of a partition-based method with BCUT descriptors [69] to design an NMR screening library has recently been described [70]. 

Fluorocarbons and fluoropolymers have been in commercial use for over half a century and have found their way into a diverse array of products. The members of this array are too numerous to hst but they include nonstick coatings for cookware, construction materials, carpets, textiles, paints, electronic materials, household cleaners and personal hygiene products. As fluorocarbons are expensive compared to their hydrocarbon analogues, they are chosen carefully and usually to fill a void in a product attribute that simply cannot be accommodated by another material. The attributes typically afforded by the use of fluorocarbons are repellency, lubricity, chemical and thermal inertness, and low dielectric constant, in regards to which fluorocarbons are unique among their hydrocarbon counterparts. 

Figure 6.1 A TEM image of an ultramicrotome slice of an anhydrous, porous, chondritic IDP, L2009 E2. Dark areas are mineral grains, while the light areas are void spaces. The boundary of the particle is shown by the solid line. This particle is an aggregate of minerals of diverse compositions (TEM image from L.P. Keller).

All of these external resources have relied heavily on the university as a primary source. An unfortunate consequence of these activities over the past decade has been a depletion of the academic resources that have accumulated over the past 50 years. Furthermore, the availability of useful quantities from current academic research has become less likely as modern chemical techniques and instrumentation permit studies with only a few milligrams. This is especially apparent in the natural product field, as the unique diversity inherent in that group has placed such acquisition at a premium. Market demands, nevertheless, persist and have led to the emergence of synthesis factories that prepare compounds specifically for the screening market, using conventional chemical techniques. Output has been greatly enhanced at some of these centers by adoption of modular approaches in synthesis. These sources have helped to fill the void in numbers, but have done little to enhance the level of structural diversity or the cost factor. 

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