Water accessibility

Isolation of radioactive wastes for long periods to allow adequate decay is sought by the use of multiple barriers. These include the waste form itself, the primary containers made of resistant materials, overpacks as secondary layers, buffer materials, concrete vaults, and finally the host rock or sod. Barriers limit water access to the waste and minimize contamination of water suppHes. The length of time wastes must remain secure is dependent on the regulatory limit of the maximum radiation exposure of individuals in the vicinity of the disposal site. 

Since experimental determination of intestinal absorption is quite demanding, Caco-2 cell monolayers have been successfully used to model passive drug absorption. Several models for the prediction of Caco-2 permeability using PSA were developed, including those of van de Waterbeemd et al. [5] and Palm et al. [22] who found that relationships between Caco-2 permeability and PSA is stronger than with Clog D, Krarup et al. [23] who used dynamic PSA calculated for water accessible molecular surface and Bergstrom et al. [24]. 

Mehler EL, Eichele G (1984) Electrostatic effects in water-accessible regions of proteinst. Biochemistry 23 3887-3891. 

Protein molecules contain both polar and apolar groups. For proteins dissolved in water, these apolar groups tend to be buried in the interior of the globular structure, as a result of expulsion by the surrounding water. However, other interactions, as well as geometrical constraints, interfere with the hydrophobic effect, so that a minor fraction of the water-accessible surface of the protein molecule may be apolar. Protein molecules that do not spontaneously aggregate in water do not have pronounced apolar patches at their surfaces. 

For Gdin-based agents, the relaxivity response is most often related to a change in water accessibility or to the variation of the size and consequently of the rotational correlation time of the complex. In addition to Gdm complexes, PARACEST agents are... 

S-galactosidase activity (Scheme 12) (201-203). Before the enzymatic cleavage, depending on the linker, the galactopyranose or a carbonate in bidentate coordination block the water access to the Gd111 ion. After enzymatic cleavage, one water molecule enters the inner sphere and results in an increased relaxivity. 

It is possible to modify the matrix hydrophilicity-lipophilicity balance (HLB) by using different alkyl-modified trialkoxysilanes as co-reagents with tetraethylorthosilicate (TEOS), to greatly alter (reduce) the release rate of heparin, as then water access to the entrapped drug is considerably reduced (Figure 2.10).4... 

The linear solvent strength (LSS) model combined with QSRR calculations has been applied for the prediction of retention in gradient RP-HPLC. It was established that total dipole moment (jd), electron excess charge of the most negatively charged atom (<5Mm) and water-accessible molecular surface area (Awas) exert the highest impact on the retention ... 

The authors also computed the polar parts of the van der Waals surface (Eq. 10) and the water-accessible surface (Eq. 11) using a Roche in-house program, MOLOC, and achieved relationships of similar quality to Young s model (Eq. 1) ... 

The authors increased the quality of their correlation by replacing the molecular weight with the water-accessible volume, which gave a slightly higher correlation coefficient than did Eq. 23 ... 

Kaliszan and Markuszewski [23] Salminen et al. [41] Lipophilicity, size, and water-accessible volume log fciAM, molecular volume, and an ionization variable... 

BBB permeability increases with increasing lipophilicity and reducing size and water-accessible volume. 

Livingstone, J.R., R.S. Spolar, and M.T. Record, Jr. 1991. Contribution to the thermodynamics of protein folding from the reduction in water-accessible nonpolar surface area. Biochemistry 30 4237 1244. 

The introduced cysteine residues are found in one of three possible environments (1) on the water-accessible surface, (2) within the protein interior, or (3) at the protein-lipid interface (Karbn and Akabas, 1998). 

Residues lining water-accessible binding sites will react with charged, hydrophilic, and sulfhydryl-specific reagents and with residues that face the interior of the protein or the lipid bilayer will not be accessible. 

Williams DB, Akabas MH. 1999. y-Aminobutyric acid increases the water accessibility of M3 membrane-spanning segment residues in y-aminobutyric acid type A receptors. Biophys J 77 2563-2574. 

Near San Zulian. You decide where to let me off. San Zulian parish is just north of the Piazza, in an area so congested that there is little water access and the campo itself is almost nonexistent. Raffaino Sciara, chief secretary to the Council of Ten, would naturally want to live close to the Doges Palace, where he spends most of his waking hours. At two hundred ducats a handshake, he could afford to. 

This part of the case study was broken into two sections, the original descriptor set (2,125,127) (Hansch descriptors) and a new set of descriptors calculated in MOE (6) (MOE descriptors). The MOE Descriptors were calculated for molecules assigned Gasteiger (70) partial charges in the MMFF (46-52). The new descriptor set is constructed of three properties. The water accessible surface area (ASA) calculated using a radius of 1.4 A for a water molecule and the... 

Analysis of the Hansch descriptors illustrates that increasing the lipophilicity property for this series of compounds will increase the bioactivity in a more dramatic fashion than increasing the Tafts steric parameter. Increasing the water accessible surface area (MOE descriptor) will increase the bioactivity of the compounds. But there is more than just adding lipophilicity and water accessible surface area to the molecules to increase binding affinity. A comparison of the substituents to the bioactivities illustrates that the bulkier X and Y groups increase bioactivity in conjunction with atomic partial charge distribution of the substituents. 

The C5+, and smeta values were experimentally determined, and the ASA, vdW and logP (o/w) were determined in MOE. [7t = lipophilicity parameter o+ = Hammett constant for ben-zylic cations Esmeta = Tafts steric parameter ASA = water accessible surface area vol = van der Waals volume logP (o/w) = log of the octanol/water partition coefficient.]... 

A modification of the atomic approach was also proposed by Gaillard et al. using molecular lipophilicity potential (MLP) as a 3D source of two lipophilicity parameters calculated from the water-accessible surface, namely a hydrophobic parameter expressed as the sum ofthe positive lipophilicity potential (EM LP+) and a polar parameter expressed as the sum of the negative lipophilicity potential (EMLP—)... 

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