Combinatorial research

The discovery of Redfield s paper had an immediate impact on combinatorial research. Various expository papers appeared, interpreting Redfield s results in modern notation (see, for example, [HarF67c], [FouH63], [FouH66]), and soon the effects of his discovery began to become apparent. 

The above list of modifiers unambiguously shows their large diversity. There are examples indicating that the best results can be achieved by combination of several modifiers [22]. Consequently, catalyst modification is an excellent field for combinatorial research provided a library optimization method is available. 

While most combinatorial researches reported up to now involve the use of GA, using the traditional crossover and mutation operators (e.g. WGS 1), it has also been proposed to design new operators for each specific application, to improve search efficiency by means of knowledge extraction [32]. Hence, new methods that combine ES with a knowledge extraction engine have been reported recently within the field of heterogeneous catalysis, such as mining association rules [12, 18, 30, 33] and neural networks [19, 29, 34]. 

Solid-phase synthesis of peptides was pioneered by Bruce Merrifield in the early 1960s. This work, for which he won the Nobel Prize in 1984, set in motion the modern approach to drug discovery called combinatorial chemistry. Through combinatorial chemistry, millions of compounds are generated by the synthesis of libraries on solid supports and screened for therapeutic activity by high-throughput assays. The importance of this work is attested by the numerous combinatorial research units that are now an integral part of most major pharmaceutical companies. 

Does academic combinatorial research aim only at discovering entirely new materials ... 

Combinatorial catalyst research will help satisfy the demands placed on new process technologies. As 90% of all production processes work with catalysts to ensure efficient, cost-effective conversion, they have a key role to play. In future, combinatorial research will generate what was once mainly acquired empirically. With combinatorial methods, many possible design variants can be tested very reliably and within a short time, to locate their optimum behavior. The information gathered includes the type and structure of the required catalyst carrier as well as catalytic conversion rates. To achieve this, modern machines with a very high throughput/screening rate... 

The research of Mallouk and Smotkin [45] considered combinatorial catalyst development methods. In the combinatorial research, the tools of electrochemical analysis (steady-state and dynamic voltammetry, chronoamperometry, scanning electrochemical microscopy, spectroelec-trochemistry, complex impedance analysis) are used to test electrochemical cell. These tools allow the kinetic and mechanistic studies not readily available in nanoelectrochemistry. The research concentrated on improving the metallic catalyst, and also optimizing the interfacial contact and utilization. 

Large chemical databases, combinatorial libraries, and data warehouses have become indispensable tools in modem chemical research. Accordingly, stmctural information must be stored in these databases and searched in an appropriate manner. 

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

For more than two decades researchers have attempted to overcome the inadequacies of Flory s treatment in order to establish a model that will provide accurate predictions. Most of these research efforts can be grouped into two categories, i.e., attempts at corrections to the enthalpic or noncombinatorial part, and modifications to the entropic or combinatorial part of the Flory-Huggins theory. The more complex relationships derived by Huggins, Guggenheim, Stavermans, and others [53] required so many additional and poorly determined parameters that these approaches lack practical applications. A review of the more serious deficiencies... 

Combinatorial chemistry constitutes a branch of the molecular sciences, providing an array of concepts and methods to solve molecular optimization problems (in drug research and beyond) more rapidly and efficiently than classical synthetic approaches. 

---