Properties distributions

Theoretically, the effects of the manufacturing process on the material property distribution can be determined, shown here for the case when Normal distribution applies. For an additive case of a residual stress, it follows that from the algebra of random variables (Carter, 1997) ... 

The pace of development has increased with the commercialization of more engineering plastics and high performance plastics that were developed for load-bearing applications, functional products, and products with tailored property distributions. Polycarbonate compact discs, for example, are molded into a very simple shape, but upon characterization reveal a distribution of highly complex optical properties requiring extremely tight dimension and tolerance controls (3,223). 

The science dealing with the properties, distribution, and circulation of water. 

Oprea TI. Property distributions of drug-related chemical databases. / Comput-Aided Mol Des 2000 14 251-264.55. 

B. Measurement of Property Distributions for Copolymers. Figure 12 shows chromatograms of typical products in the copolymerization study (Column Code B2). Since the detector is responding to concentration, composition, and periiaps sequence length, the direct single detector interpretation as described for PMMA is not immediately applicable here. Tacticity variation is yet another consideration but ]s assumed of sa ond order importance for th samples (22). 

V. Copolvmerization Kinetics. Qassical copolymerization kinetics commonly provides equations for instantaneous property distributions (e.g. sequence length) and sometimes for accumulated instantaneous (i.e. for high conversion samples) as well (e.g. copolymer composition). These can serve as the basis upon whkh to derive nations which would reflect detector response for a GPC separation based upon properties other than molecular weight. The distributions can then serve as c bration standards analagous to the use of molecular weight standards. 

Another sampling effect which deserves mention is that since the molecular weight distribution shifl towards higher molecular weights with conversion, a slice will not in general contain proportionate amounts of polymer from all conversions. This dufting can be accounted for in the theoretical predictions by incorporating it into cumulation of the instantaneous property distributions (e.g. Equation 8). 

Phrasing kinetic models in terms of instantaneous property distributions which are summed to provide distributions at any conversion is then highly rewarding. The variation of individual concentrations with time from the GPC readily provides significant insight into the model requirements. 

Feher, M., Schmidt,. M. Property distributions differences between drugs, natural products, and molecules from combinatorial chemistry. J. Chem. Inf. Comput. Sci. 2003, 43, 218-227. 

From an analysis of the key properties of compounds in the World Dmg Index the now well accepted Rule-of-5 has been derived [25, 26]. It was concluded that compounds are most Hkely to have poor absorption when MW>500, calculated octanol-water partition coefficient Clog P>5, number of H-bond donors >5 and number of H-bond acceptors >10. Computation of these properties is now available as a simple but efficient ADME screen in commercial software. The Rule-of-5 should be seen as a qualitative absorption/permeabiHty predictor [43], rather than a quantitative predictor [140]. The Rule-of-5 is not predictive for bioavail-abihty as sometimes mistakenly is assumed. An important factor for bioavailabihty in addition to absorption is liver first-pass effect (metaboHsm). The property distribution in drug-related chemical databases has been studied as another approach to understand drug-likeness [141, 142]. 

Oprea, T. L. Property distribution of drug-related chemical databases. J. Comput.-Aided Mol. Des. 2000, 14, 251-254. 

State-of-the-art polymeric materials possess property distributions in more than one parameter of molecular heterogeneity. Copolymers, for example, are distributed in molar mass and chemical composition, while telechelics and macromonomers are distributed frequently in molar mass and functionality. It is obvious that n independent properties require n-dimensional analytical methods for accurate (independent) characterization of the different structural parameters. 

Overall, several useful concepts emerge from these analyses. Different targets and routes of administration may require biased property distributions and screening libraries for successful lead optimization. This could influence the eventual chances of project success and should be taken into account early by project leaders. Once more, optimization focused on potency has been shown again to lead to larger molecules which increases the potential for poor ADME properties. The extent of any ADME issues would of course depend on the structure of lead molecule. Finally, larger, more lipophilic molecules historically have an increased rate of failure in the clinic. 

Graham D, Reed ML, Patterson BD, Hockley DG. 1984. Chemical properties, distribution, and physiology of plant and algal carbonic anhydrase. Annals of the New York Academy of Science 429 222-237. 

Oprea, T.I. Property distribution of drug-related chemical databases. 

The compound property distribution also impacts the analysis. For example, in Figure 3.2, solubility appears to have a relatively low weight (close to the center) this is not because solubility does not impact exposure but is due to the fact that all compounds tested had a low solubility and therefore this parameter could not discriminate compounds. 

Definition of a Complex Polymer. A simple polymer is one vrtiich has at most one broad molecular property distribution (e.g., a broad molecular weight distribution). A complex polymer is one which has two or more broad molecular property distributions (e.g., a broad molecular weight distribution and a broad copolymer composition distribution) ( ). Properties such as molecular weight and composition, Aiich can be in so much variety in a polymer that they must be described as a distribution, are here termed "distributed properties". It is the presence of simultaneous breadth (i.e., variety) in more than one distributed property which is the defining characteristic of a "complex" polymer and the source of analysis difficulties. 

Figure 1 Property distribution in a linear homopolymer molecular weight distribution of polystyrene (styrene units represented by "A")-...

Figure 2 Property distributions in a linear copolymer composition distribution, molecular weight distribution and sequence length distribution of poly styrene-co-n-butyl methacrylate). (Styrene units are represented by "A and n-butyl methacrylate units by B".)...

There have been many studies directed at using adsorption and re versed-phase HPLC to separate copolymers by composition (1.-3) interacting problems associated with these approaches ares o The presence of one property distribution interferes with separation on the basis of the other. For example, in adsorption chromatography, the degree of adsorption can be affected by both the molecular weight and by the composition of the molecule. For a linear copolymer, adequate fractionation requires that the ccmposltlon differences completely dominate. 

Cross-Fractionation. Complex polymers contain more than one broad property distribution, if molecular weight and composition are the only two property distributions present then an example of cross-fractionation would be the separation of the polymer first according to molecular weight and the separation of each single molecular weight fraction obtained according to composition. This cross-fractionation provides a two-dimensional answer to a two-dimensional distribution problem. It has typically been accomplished for polymers using solvent/non-solvent precipitation. 

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