Small Molecular Structures

For example, see chapters 8-12 in Computer-Assisted Lead Finding and Optimization, eds. H. van de Waterbeemd, B. Testa, and G. Folkers, Wiley-VCH, Basel, 1997. 

Proprietary technology is reported to exist that is an order of magnitude faster, S. Teig, personal communication. 

The most fundamental assertion underlying combinatorial chemistry is that a very large number of different molecular structures is possible. This fact raises the obvious question, How many different molecules are possible It is a simple question but it does not have a simple answer. 

Molecule enumeration has been discussed in the scientific literature since Cayley proposed an approach to the problem in 1875. The last 120 years have seen the periodic resurgence and decline of interest in this topic. The 1930s saw breakthroughs in the field of acyclic molecule counting by Blair and Polya. A profound resurgence of interest occurred in 

1965-1975 which was oriented mainly toward structural elucidation for analytical purposes. The current (1990s) interest in combinatorial chemistry is oriented toward drug discovery and refinement, which is a new twist on this very old problem. The bottom line is that some very restricted special cases have been solved, but so far no one has offered a viable approach to solving the general problem. 

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Weininger, D. Combinatorics of small molecular structures. In Encyclopedia of Computational Chemistry, Vol. 1,... 

Xitro and Nitraso Dyes. These dyes are now of only minor commercial importance, hut are of interest for their small molecular structures. The most important nitro dyes are the nitrodiphcnylamines. Their small molecules arc ideal for penetrating dense libers such as polyester, and are therefore used as disperse dyes for polyester. All the important dyes are yellow. Although the dyes are not terribly strong (fW- 20- 000). they are cosi-effective hecatise of their easy synthesis from inexpensive intermediates... 

These dyes are now of only minor commercial importance, but are of interest for their small molecular structures. The early nitro dyes were acid dyes used for dyeing natural animal fibers such as wool and silk. They are nitro derivatives of phenols, e.g., picric acid (4) or naphthols, e.g., C.I. Acid Yellow 1, 10316 [846-70-8] (5). 

The difference between citronellol and citronellal is typical of that between an alcohol and an aldehyde. Although they are clearly related in odor, the aldehyde is, as we would expect from quite a small molecular structure, very much more powerful and harsh. In hydroxycitronellal the addition of an—OH and—H across the double bond (in effect by adding a molecule of water, a process known as hydration) produces an alcohol group near to the other end of the molecule, away from the aldehydic group. The material still maintains some of its aldehydic character but now, in addition, has some of the softness and floral character associated with an alcohol. The presence of more than... 

Experimental structures are often the basis for computational studies they are used as input structures for structure optimizations and conformational searches, for the parameterization and validation of force fields and for analyzing the effects of crystal lattices. More than 200,000 experimental structures have been reported, and the majority are found in the Cambridge Structural Data Base (CSD, small molecular structures which include carbon atoms) the Inorganic Crystals Structure Database (ICSD) and the Protein Data Base (PDB this database includes X-ray as well as optimized structures based on NMR data). 

The Cambridge Crystallographic Data Center (http //www.ccdc.cam.ac.uknow provides a computerized database of more than 200,000 small molecular structures. In addition to this extensive structural database, the Cambridge group has developed a suite of programs for systematic structure search and retrieval. The most unique aspect of these programs is that database search queries can specify desired structures in three dimensions. 

The asymmetric insertion of a-diazoesters into the O—H bond of water provides an extremely simple approach for the synthesis of chiral a-hydroxyesters in an efficient and atom-economical way. The challenges of asymmetric O—H insertion of water are mainly attributed to two considerations first, the active metal carbene intermediates are generally sensitive to water and secondly, the small molecular structure of water makes chiral discrimination quite difficult. Zhou and co-workers discovered a highly enantioselective O—H insertion of water catalyzed by chiral spiro Cu [112] and Fe catalysts [111]. Under mild conditions, both Cu andFe complexes of ligand (S, 5,5)-23a... 

The first X-ray diffraction photograph ever taken was from copper sulphate by Friedrich and Knipping at von Laue s suggestion in 1912. In the following year W. L. Bragg deduced the crystal structure of sodium chloride from Laue photographs. A variety of relatively small molecular structures were then solved at an increasing rate. 

The importance of Chen and Yang s stndy [70] is not only because of the more accurate calculations for the unified mechanism, but also because it presents the promising prospect that with relatively small molecular structures and reasonable model chemistry, ab initio methods can provide reliable quantitative or semiquantitative results in the complicated studies of gas-carbon reactions. 

Biochemical reactions involve small molecular structures... 

Most elements are metals, bonding to themselves only in infinite three-dimenaonal arrays, and the metallic bonds in these arrays are not localized between pairs of atons. This means that they cannot be selectively broken and reformed during biochemical processes, and small molecular structures with metal-metal bonds are almost unknown. We have 10 metals left in our list sodium, magnesium, aluminum, potassium, titanium, chromium, manganese, cobalt, nickel, and iron almost aU of the 63 elanents that we eliminated earlier as being too rare are also metals. 

A pervasive pattern apparent in both small-molecule chemistry as well as macromolecular science is the significant role that architecture plays in the determination of new properties. As early as 1825, Swedish chemist Jacob Berzelius clearly demonstrated that small molecular structures possessing identical elemental compositions, but different spatial arrangements, invariably differed in raie or more... 

Combinatorial Chemistry Combinatorial Libraries Structure-Activity Analysis Combinatorics of Small Molecular Structures Competitive Molecular Field Analysis (CoM-FA) Drug Design Molecular Docking and Structure-based Design Quantitative Structure-Activity Relationships in Drug Design Quantitative Structure-Property Relationships (QSPR). 

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