Structure lead crystals

An impressive example of the application of structure-based methods was the design of a inhibitor of the HIV protease by a group of scientists at DuPont Merck [Lam et al. 1994 This enzyme is crucial to the replication of the HIV virus, and inhibitors have bee shown to have therapeutic value as components of anti-AIDS treatment regimes. The star1 ing point for their work was a series of X-ray crystal structures of the enzyme with number of inhibitors boimd. Their objective was to discover potent, novel leads whid were orally available. Many of the previously reported inhibitors of this enzyme possessei substantial peptide character, and so were biologically unstable, poorly absorbed am rapidly metabolised. 

How do the mutations identified by phage display improve binding specificity There is as yet no direct stmctural information on the phage-selected inhibitors however they can be modeled using data from the crystal structures of other Kunitz domains bound to serine proteinases. These studies lead to the conclusion that the mutations identified by phage display improve binding specificity by maximizing complementarity between the... 

The crystal structure of the potassium salt of 1,3,5,7-tetramethylcyclootatetraene dianion has been determined by X-ray dififaction. ° The eight-membered ring is planar, with aromatic C—C bond lengths of about 1.41 A without significant alternation. The spectroscopic and structural studies lead to the conclusion that the cyclooctatetraene dianion is a stabilized delocalized structure. 

The crystal structure of many compounds is dominated by the effect of H bonds, and numerous examples will emerge in ensuing chapters. Ice (p. 624) is perhaps the classic example, but the layer lattice structure of B(OH)3 (p. 203) and the striking difference between the a- and 6-forms of oxalic and other dicarboxylic acids is notable (Fig. 3.9). The more subtle distortions that lead to ferroelectric phenomena in KH2PO4 and other crystals have already been noted (p. 57). Hydrogen bonds between fluorine atoms result in the formation of infinite zigzag chains in crystalline hydrogen fluoride... 

Generally the name of a compound should correspond to the most stable tautomer (76AHCS1, p. 5). This is often problematic when several tautomers have similar stabilities, but is a simple and reasonable rule whose violation could lead to naming phenol as cyclohexadienone. Different types of tautomerism use different types of nomenclature. For instance, in the case of annular tautomers both are named, e.g., 4(5)-methylimidazole, while for functional tautomerism, usually the name of an individual tautomer is used because to name all would be cumbersome. In the case of crystal structures, the name should reflect the tautomer actually found therefore, 3-nitropyrazole should be named as such (97JPOC637) and not as 3(5)-nitropyrazole. 

In most cases crystal densities differ from the densities of amorphous polymers. This leads to differences in refractive index, which in turn cause scatter of light at boundaries between amorphous and crystalline zones. Such materials are opaque except in certain instances where the crystal structure can be carefully oriented to prevent such scatter of light. 

The formulated principals correlating crystal structure features with the X Nb(Ta) ratio do not take into account the impact of the second cation. Nevertheless, substitution of a second cation in compounds of similar types can change the character of the bonds within complex ions. Specifically, the decrease in the ionic radius of the second (outer-sphere) cation leads not only to a decrease in its coordination number but also to a decrease in the ionic bond component of the complex [277]. 

In general, increasing the temperature within the stability range of a single crystal structure modification leads to a smooth change in all three parameters of vibration spectra frequency, half-width and intensity. The dependency of the frequency (wave number) on the temperature is usually related to variations in bond lengths and force constants [370] the half-width of the band represents parameters of the particles Brownian motion [371] and the intensity of the bands is related to characteristics of the chemical bonds [372]. 

In other cases, if the fluorination process leads to cardinal changes in the crystal structure of the initial oxide compounds, new compounds with polar structures can be obtained. A demonstrative example of such materials are compounds that belongs to the system Na5(W3 xNbx)09..xF5+x and that have chiolite-type structures, when neither pure fluoride nor oxide display any ferroelectric properties [393 - 395]. 

An irreversible extinction of the SHG signal at 150-200°C is observed for a number of other fluoride and oxyfluoride compounds of tantalum and niobium that crystallize in centrosymmetric space groups. This phenomenon is especially typical for the compounds prepared by precipitation from solutions [206]. The appearance of the weak SHG signal for such compounds is related to imperfections in their crystal structure and the creation of dipoles. Nevertheless, appropriate thermal treatment improves the structure and leads to the disappearance of dipoles and to the irreversible disappearance of the corresponding SHG signal. 

The crystal structure of MsM OF compounds, where M = NH4, K, Rb, is made up of infinite chains of oxyfluoroniobate octahedrons that are similar to MNbOF4 chain-type compounds. Infinite chains are separated by isolated complexes NbFy2, whose structure is similar to that found in the island-type compound K2NbF7. The structure of the M5Nb30Fi8 compounds was described and discussed in Chapter 3.2. Due to the separation of the chains, the displacement of the niobium ion is in the same direction in all chains. The above displacement leads to a spontaneous polarization value that is as high as 4-5 pC/cm2. 

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