Placement of Water Molecules

Another approach is to first place the solute molecule and ions in the simulation box. The box is then divided into cubes conq atable in size to the diameter of the water molecule, and water molecules, in random orientation, are placed into each cube not containing portions of solute or ion. This approach creates larger voids near the surface of the solute molecule because cube division always begins at one face of the box. An attractive alternative for regular-shaped solutes (e,g., canonical A-, B-, Z-DNA) is to extend the cubes outward from the surface of the solute. This alternative requires more equilibration than is needed to start from a preequilibrated 216-water box because of the inherent order in the system created by ordered cubes. Unlike the method featuring a preequilibrated water box, the latter approaches need time to establish intermolecular water structure. 

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Still, there are several recommendations that could help consider water molecules and solvation effects in virtual screening. When using information on water molecules derived from X-ray data, it is very important to verify their position in the electron density directly, as the placement of water molecules may be arbitrary if not in the focus of the crystallographer. In addition, it is advisable to check whether the water molecule under consideration is confirmed by interaction partners in the stmcture. Computer simulations might help judge the mobility, ordering, and synergetic effects of specific water molecules. 

Hydrate isomers isomers of a complex that differ in the placement of water molecules in the complex. (23.5)... 

Figure 3.11 The coordination of water molecules abotit the Na atom situated above the basal tetrahedral oxygen atoms. The left view shows an oblique view of the interlayer water structure and the right is a projection onto the layer of the same Na-water coordination arrangement showing the placement of the Na atoms above the tetrahedra of the adjacent silicate layer. In these illustrations, only the ions and the coordinating water oxygen atoms are shown hydrogen atoms have been omitted.

Precise placement of metal complexing sites within the infrastructure of a cascade molecule is of importance from a variety of perspectives. In the construction of the above noted Micellane family (cf. Sect. 3.1), we reported the construction of dendrimers with four alkyne moieties at sites equidistant from each other in the interior (17, Fig. 8) [60]. These were treated with decaborane (B10H14) to afford 1,2-dicarba-closo-dodecaboranes (o-carboranes) [71]. Rendering boron clusters soluble in water is of interest because of their use in cancer treatment by Boron Neutron Cancer Therapy. First and second generation water-soluble dendrimers containing four and twelve precisely located boron cluster sites, respectively, were synthesized (e.g., 18). These water soluble dendrimers and their precursors were characterized by 13C-, and nB-NMR spectroscopy (Fig. 8). 

While there have been a considerable number of structural models for these multinuclear zinc enzymes (49), there have only been a few functional models until now. Czamik et al. have reported phosphate hydrolysis with bis(Coni-cyclen) complexes 39 (50) and 40 (51). The flexible binuclear cobalt(III) complex 39 (1 mM) hydrolyzed bis(4-nitro-phenyl)phosphate (BNP-) (0.05 mM) at pH 7 and 25°C with a rate 3.2 times faster than the parent Coni-cyclen (2 mM). The more rigid complex 40 was designed to accommodate inorganic phosphate in the in-temuclear pocket and to prevent formation of an intramolecular ju.-oxo dinuclear complex. The dinuclear cobalt(III) complex 40 (1 mM) indeed hydrolyzed 4-nitrophenyl phosphate (NP2-) (0.025 mM) 10 times faster than Coni-cyclen (2 mM) at pH 7 and 25°C (see Scheme 10). The final product was postulated to be 41 on the basis of 31P NMR analysis. In 40, one cobalt(III) ion probably provides a nucleophilic water molecule, while the second cobalt(III) binds the phosphoryl group in the form of a four-membered ring (see 42). The reaction of the phosphomonoester NP2- can therefore profit from the special placement of the two metal ions. As expected from the weaker interaction of BNP- with cobalt(in), 40 did not show enhanced reactivity toward BNP-. However, in the absence of more quantitative data, a detailed reaction mechanism cannot be drawn. 

The gels can incorporate even polymers such as, for example, water-soluble polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), and polypropyl-eneglycol (PPG). For the PE0/V205 system the interlayer broadening achieved 13.2 A, which corresponds to more probable placement of the polymer molecules along the layers [1373] (Fig. 11.1 b). 

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