Predicting partition properties

Partition data for compounds containing quaternary pyridinium-type moieties. 

Unfortunately, the same physicochemical characteristics that allow for successful chemical delivery also complicate the development of acceptable pharmaceutical formulations. The increased lipophilicity allows partition into deep brain compartments, but also confers poor aqueous solubility. The oxidative lability, which is needed for the lock-in mechanism, and the hydrolytic instability, which releases the modifier functions or the active drug, combine to limit the shelf-life of the CDS. Cyclodextrins may provide a possible solution. They are torus-shaped oligosaccharides that contain various numbers 

The structural optimization of the X-ray structure and that of the isolated molecule was done as follows [157] The X-ray structure was fixed as indicated by the experimental coordinates, but all C-H and 0-H bond lengths, angles, and torsion angles were optimized. This was needed since the X-ray data indicate only the location of the heavy atoms, and to produce a consistent structure, the 

The X-ray structure seems to be more symmetrical than that obtained for the AMI optimized individual molecule. The variability among various inner diameters is very small, averaging 7.82 A, while the diameters of the AMI optimized structure vary between 7.1 A, and 8.4 A, averaging out to 7.68 A. Similarly, the outer diameters show much more variability for the isolated, optimized molecule. The height or thickness of the molecule shows significantly less variability between the two structures. Contrary to the general concept, the X-ray structure does not look cone-like at all. It is more like a doughnut, while the isolated AMI structure shows cone-like tendencies. 

The experimental heavy atom X-ray frame was kept rigid, but all 0-H and C-H bond lengths and bond angles were optimized using AMI. Heavy atom X-ray frame from [163]. Heavy atom X-ray frame from [162]. AMI energies of MM2 optimized stmctures. Heavy-atom X-ray frame from [164]. 

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Two approaches to quantify/fQ, i.e., to establish a quantitative relationship between the structural features of a compoimd and its properties, are described in this section quantitative structure-property relationships (QSPR) and linear free energy relationships (LFER) cf. Section 3.4.2.2). The LFER approach is important for historical reasons because it contributed the first attempt to predict the property of a compound from an analysis of its structure. LFERs can be established only for congeneric series of compounds, i.e., sets of compounds that share the same skeleton and only have variations in the substituents attached to this skeleton. As examples of a QSPR approach, currently available methods for the prediction of the octanol/water partition coefficient, log P, and of aqueous solubility, log S, of organic compoimds are described in Section 10.1.4 and Section 10.15, respectively. 

Dickhut, R.M., Miller, K.E., Andren, A.W. (1994) Evaluation of total molecular surface area for predicting air water partitioning properties of hydrophobic aromatic chemicals. Chemosphere 29, 283-297. 

Basak, S. C., Mills, D. Prediction of partitioning properties for environmental pollutants using mathematical structural descriptors. ARKIVOC 2005, 2005(b), 60-76. 

Environmental Fate. Experimental data are available regarding the transport and partitioning properties of chloroform in surface waters (Bean et al. 1985 Clark et al. 1982 Class and Ballschmidter 1986 Dilling 1977 Ferrario et al. 1985 Piwoni et al. 1986 Sawhney 1989). Chloroform partitions mainly into the atmosphere and into groundwater. Empirical measurements or model predictions on half-disappearance times in such media as soil could not be identified in the literature. Chloroform can be transported long distances in air. Data are available regarding the degradation of chloroform in the... 

The prediction of the partition properties of peptide molecules is difficult, owing to their conformational flexibility, and the possible presence of multiple intramolecular hydrogen bonds and ionizable groups. Richards and coworkers (40-42) were the first to consider explicitly the effects of the population of accessible conformational minima in both phases. These types of calculation are, however, computationally intensive. The introduction of the solvent-accessible surface area in the prediction of log Poct for steric isomers (43,44) also constitutes a promising approach. 

Dickhut, R. M., K. E. Miller, and A. W. Andren, Evaluation of Total Molecular Surface Area for Predicting Air-Water Partitioning Properties of Hydrophobic Aromatic Chemicals. Chemosphere, 1994 29, 283-297. 

Recent studies showed that amphiphilic properties have to be taken into account for most water-soluble monomer units when their behavior in water solutions is considered. The amphiphilic properties of monomer units lead to an anisotropic shape of the polymer structures formed under appropriate conditions, which is confirmed both by computer simulation and experimental investigations. The concept of amphiphilicity applied to the monomer units leads to a new classification based on the interfacial and partitioning properties of the monomers. The classification in question opens a broad prospective for predicting properties of polymer systems with developed interfaces (i.e., micelles, polymer globules, fine dispersions of polymer aggregates). The relation between the standard free energy of adsorption and partition makes it possible to estimate semiquantitatively the distribution between the bulk and the interface of monomers and monomer units in complex polymer systems. 

Dai, J., Sun, C., Han, S., and Wang, L., QSAR for polychlorinated organic compounds (PCOCs). I. Prediction of partition properties for PCOCs using quantum chemical parameters, Bull. Environ. Contamination Toxicol., 62, 530-538, 1999. 

Environmental fate models make use of chemical properties to describe transfer, partitioning, and degradation (Mackay et al. 1992a Cahill et al. 2003). For organic chemicals, quantitative structure-property relationships (QSPRs) may be used to predict partitioning from physical-chemical properties, such as Kow and Kov Such properties may also allow for a prediction of the transfer of chemicals between compartments. Recently, some successful attempts have also been made to predict persistency of chemicals (Raymond et al. 2001), although this mainly concerns... 

The partitioning of trace elements between the soil and soil solution determines their mobility and bioavailability. However, predicting the properties of soil... 

Interpretation of urinary excretion data following topical application Is presented for 9 compounds. It Is shown that the model has predictive potential based upon recognized cutaneous biology and penetrant physical chemistry, In particular the diffusive and partitioning properties of the substrate. Refinements and developments of the approach (e.g., to multiple exposure and competitive surface removal situations) are Indicated and discussed. 

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