Chemical complementarity

Structural formulas in such studies, together with relevant measures of structural similarity, has recently been published by Willett [61]. 

At the molecular level, shape is now reali d to be one of the most fundamental concepts of chemistry, even though it may be difficult to quantify [67], In 1980 the first quantum-mechanical measure of shape similarity for molecules was put forward by Carbo et al. [68]. This measure, which was intended to be of special use in molecular design studies, proved to be of seminal influence. For any two molecules, M and N, the similarity, S ns was defined as the ratio 

Classifications that enable us to partition chemical entities into mutually disjoint sets, that is to divide them up in such a way that each entity belongs to one and only one subset, are clearly of fundamental importance to chemists. In mathematical terminology this situation is described by saying that an equival- 

In cases (i) and (ii) the relationship R is said to generate a partially ordered set or poset, whereas in case (iii) a totally ordered set is produced. Let us now move on to some chemically relevant instances. 

Such weaker relationships are usually represented in the physical sciences by so-called Hasse or chain diagrams. These are constructed by depicting set members, s , as points, a , in some geometrical space and then connecting pairs of points that satisfy the relationship R. Chain diagrams have been widely employed in the chemical context to order members of chemical series, such as 

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Complementarity. To a first approximation, complementarity should take two forms (Fig. 1). Firstiy, the shape and size of the receptor cavity must complement the form of the substrate. Secondly, there must be a chemical complementarity between the binding groups lining the interior of the cavity and the external chemical features of the substrate (15). 

HIV Protease. Docking of the 3D structures of the Cambridge Structural Database into the HIV protease binding site, by shape and to some extent by chemical complementarity, was performed with an early version of the... 

Tulevski GS, Miao Q, Afzali A, Graham TO, Kagan CR, Nuckolls C (2006) Chemical complementarity in the contacts for nanoscale organic field-effect transistors. J Am Chem Soc 128 1788-1789... 

These complementarity rules owe their discovery to the chemical analysis of DNA by Chargaff and associates (3). The DNA from many different organisms shows the same patterns of base composition, namely A and T are always present in equal quantities, as are G and C. The immediate corollary of this observation, that a purine base (R) exists for every pyrimidine base (Y) and vice versa, led Watson and Crick to propose that two helical strands in DNA are held together by specific, intermolecular purine-pyrimidine (R Y) interactions (4). In turn, this unique chemical complementarity of the double-helical structure, proved to be a major breakthrough to understand the self-recognition and self-reproduction of DNA and forms the cornerstone of structmal biology as we know it today, more than half a century later. 

We have suggested through modeling that Cm derivatives should be inhibitors of the HIVP due to their steric and chemical complementarity with the active site. We have demonstrated that this is the case and that this behavior is consistent with a qualitative analysis of hydrophobic surface transfer in model complexes. 

Lenhof [47] has developed an approach for docking based on the identification of points on the surface of each molecule that could be equivalenced in a close-packed association. The search for possible rigid-body associations is then speeded up by considering which sets of three points on one molecule could be equivalenced to three points on the other molecule. Suitable docked complexes are then scored in terms of the geometric match between atoms followed by consideration of the chemical complementarity of the match. Trials with docking starting from unbound components showed that for several, but not all, systems the method yielded lists of a few complexes (<10) one of which was dose (<4A rmsd) to the native. This method has been extended to include a treatment of side-chain flexibility in a subsequent screening that is described in 6.6 below [48]. 

Tfl is its freezing point. With the use of Eq. (3.2), only the freezing point and heat of fusion of an impurity is needed to compute its segregation between the liquid and crystalline phase. However, the relative steric and chemical complementarity of the impurity and solute in the solid phase is not taken into consideration, and as a result, only a few systems conform to this elementary relationship. 

SANDOCK This tool uses both shape and chemical complementarity to dock the Ugand into the 17... 

Alternatively, the iminium-activation strategy has also been apphed to the Mukaiyama-Michael reaction, which involves the use of silyl enol ethers as nucleophiles. In this context, imidazolidinone 50a was identified as an excellent chiral catalyst for the enantioselective conjugate addition of silyloxyfuran to a,p-unsaturated aldehydes, providing a direct and efficient route to the y-butenolide architecture (Scheme 3.15). This is a clear example of the chemical complementarity between organocatalysis and transition-metal catalysis, with the latter usually furnishing the 1,2-addition product (Mukaiyama aldol) while the former proceeds via 1,4-addition when ambident electrophiles such as a,p-unsaturated aldehydes are employed. This reaction needed the incorporation of 2,4-dinitrobenzoic acid (DNBA) as a Bronsted acid co-catalyst assisting the formation of the intermediate iminium ion, and also two equivalents of water had to be included as additive for the reaction to proceed to completion, which... 

In fact, an emerging field of nanoscale science is envisaged in molecular capsules which can host guest molecules through noncovalent interactions. These synthetic molecular receptors exert their peculiar activity upon the conjugation of parameters such as size, shape, and chemical complementarity and are proposed for applications in catalysis of chemical reactions and for the stabihzation of reactive species [38]. For example, hollow hydrophilic metal functionahzed nanostructures can be produced from an amphiphilic metallic diblock copolymer which supramolecularly self-assemble into monodisperse noncovalently connected micelle and can be used as nanocages [39]. 

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