Fraction of compound

The major drawback of the ElogD method is that it cannot be applied to acidic compounds ionized at pH 7.4. However, on prachcal grounds, the latter represent a minor fraction of compounds in pharmaceutical libraries and structural alerts could be developed which are used to filter acidic compounds prior to the determination of Elog D in an automated fashion. 

L Molar fraction of compound i in the liquid phase (general) —... 

Hirom [71,72] demonstrated more than three decades ago that the route of excretion of xenobiotics is dependent upon MW by testing up to 75 compounds in rat, guinea-pigs, and rabbits. Lower MW compounds (< 350) were mainly eliminated in the urine (>90%). As MW increased from 350 to 450, a sharp increase in the fraction of compound eliminated in the bile occurred, and for MW > 450, compounds were eliminated 50-100% in the bile in all three species. Smith [73] correlated the log of free metabolic and renal clearance (ml/min/kg) with log D, and found a similar relationship. Metabolic clearance increases with increasing log D, while renal clearance decreases with increasing log D. 

Figure 6. Distributions of essential computed molecular properties defining drug-likeness for selected compound sets. Shown are the fraction of compounds vs. the properties. Orange NIBR historical medicinal chemistry collection. Brown Compilation of combinatorial chemistry libraries. Dark Green Drugs (launched or Phase III listed in MDDR or CMC). Brown Compilation from combinatorial libraries. Pink Natural products of DNP. tight Green HTS hits of NIBR 2004 screens. All properties were calculated with Pipeline Pilot software www.scitegic.com).

In Eq. (C) FT j is the mass fraction of compound i in the exhaust from the test fuel, Fu, is the mass fraction of compound i in the exhaust from the base fuel, and MIR, is the maximum incremental reactivity of VOC i. Thus, a specific vehicle/test fuel combination with an RAF of 1.0 is expected to have the same contribution to ozone formation (in terms of specific reactivity, grams of 03 per gram of VOC exhaust emissions) as that vehicle operating on base gasoline. An RAF < 1.0 means that 1 g of the VOC exhaust emissions will form... 

Acid-Catalyzed Hydrolysis. In acid-catalyzed ester hydrolysis the species that undergoes the rate-determining step is the protonated ester (Fig. 13.10). When the molecule is in this protonated form, the enhanced depletion of electrons near the central carbon promotes the approach of an electron-rich oxygen of a water molecule. Hence, the hydrolysis rate depends on the fraction of compound molecules that are protonated. This fraction, in turn, depends on how strong a base the ester function is. If we define an acidity constant (see Chapter 8) for the protonated species... 

Note r = correlation coefficient n = number of compounds analyzed, p = net charge on P, Kcorr = hydrolysis rate corrected for fraction of compound sorbed to sediment. K"corr represents a sediment-catalyzed transformation and rates of hydrolysis in the overlying water phase will be much lower than predicted using these QSARs. 

A total of 163 clusters were obtained, where a cluster is a group of polymorphic crystal structures of the same compound. Of the 163 clusters, 147 contained two structures, 13 had three, and three had four structures. The authors note that these numbers are first evidence of the high frequency of polymorphism in organic crystals , although the number of clusters is a relatively small percentage of the entries in the database. The number of these clusters is probably more a measure of certain authors interest in the particular polymorphic system in question. A more realistic measure (although certainly not precise because of the caveats mentioned above) of the frequency of polymorphism in these compounds wouid be the fraction of compounds in the database known to be polymorphic, whether multiple structures have been done or not. 

Fractionation of compounds with a 20-30 C boiling point difference can be achieved by inserting all the bulbs except one into the oven, distilling... 

Fig. 2 MIE ranges for several API, in milliJoules. The chart displays the fraction of compounds in the set with MIE from 1-10, 10-30, and above 30mJ. Data courtesy of the Process Safety Laboratory, Merck and Co., Inc.

For example, in a solution containing nj moles of compound 1, moles of compound 2, and ns moles of compound 3, the mole fraction of compound 2,... 

Fraction of compound X unbound in the plasma (fu) In vivo volume of distribution (1kg) Predicted volume of distribution in humans (1kg)... 

Filters can also sorb certain organic compounds possibly resulting in reduced recovery and fractionation of compounds of interest. Cranston and Buckley (1972) compared organic-membrane, glass-fiber, and silver-membrane filters for the sorption of humic acid. Organic-membrane filters sorbed 15%, glass-fiber filters 5%, and silver-membrane filters 3% of the humic acid in the solution passed through the filters. 

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