Modeling of Inclusion by Genetic Algorithms: Application to the Beta-Cyclodextrin and Triphenylphosphine

The Cyclodextrins are of particular interest and importance in the field of inclusion and the formation of molecular complex. The aim of this work is to search by various techniques, among others: the molecular docking, the inclusion techniques, and complexations (Tail-Thread, Thread-Thread, Tail-Tail) of conformations (geometric parameters) to form inclusion complexes of beta-cyclodextrin with triphenylphosphine using an evolutionary optimization method in this case the Genetic Algorithms. The results are satisfactory. Software was designed to find an elite generation that represents the most stable complexes (minimum energy). This energy has been a determining factor and was chosen as fitness function (fitness) of the genetic algorithm. DOI: 10.4018/ijcce.2013010103 IGI GLOBAL PROOF 20 International Journal of Chemoinformatics and Chemical Engineering, 4(1), 19-36, January-June 2013 Copyright © 2013, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited. cyclodextrins, ...) Have a “cavity” allowing them to give rise to inclusion complexes. The stability of the complex is therefore based on the quality of adaptation between partners (Djedaïni-Pilard, 1990). Cyclodextrins are of particular interest because they can form inclusion complexes with a large range of guest molecules. The aim of this work is the modeling of the inclusion of guest molecules by guest molecules using an evolutionary method in this case a genetic algorithms that allow a good exploration of the search space to find the most stable complexes. An application is carried out on the inclusion of betacyclodextrins by the triphenylphosphine. PROBLEMATIC AND STATE OF THE ART In 1891, Villiers isolated for the first time a group of non-reducing oligosaccharides from the enzymatic degradation of starch by an amylase (cyclodextrin glucosyl transferase) produced by different bacilli. Villiers was isolated 3g of a crystalline substance ((C6H10O5)2 3H2O) from the digestion of 1 g of starch by a strain of micro-organisms. The products obtained have physicochemical characteristics similar to those of cellulose, so he dubs “cellulosines.” They are also called dextrins. Schardinger, 20 years later isolated the microbial strain responsible for the formation of these “cellulosines,” he calls Bacillus macerans and describes the mode of purification and preparation of these oligosaccharides. It also highlights the capacity of these dextrins to form specific adducts with di-iodine molecules. The distinction between the α-dextrin and β-dextrin is due to their difference in the crystalline complexes formed with iodine. The complex of α-dextrin is gray-green, while that formed by the β-dextrin is red-brown. It was in 1932 that Prigsheim and his team demonstrate that these products have the property to form complexes with organic molecules. French, Cramer, and Freudenberg also contributed greatly to the knowledge of cyclodextrins and elucidation of their structure during the year 30-40. Freudenberg and his team demonstrate when these oligosaccharides are composed of a chain of n units to Dglucopyranosidiques, the main fraction containing alpha and beta-cyclodextrin (with units 6 and 7 respectively). Similarly the postulate in the ability of cyclodextrins to form inclusion compounds is set. This same team discovered in 1948 the γ-cyclodextrin (composed to 8 glucose units) and determines its structure completely (Freudenberg, 1953). In early 1950, teams of French and Cramer studied extensively the enzymatic production of cyclodextrins, their purification, and physicochemical characterizations. Property of cyclodextrins to form inclusion complexes became the subject of intensive study, in particular by the team Cramer (1957). Thus the first patent on the application of cyclodextrins for the formatting of a compound with biological activity was filed in 1953 (Freudenberg, 1953). From that moment, a recrudescence of the study of cyclodextrins, both in terms of their industrial production, as the exploitation of their properties, their chemical modifications or alternatively, their application areas (Duchêne, 1991). Description of Cyclodextrins These are natural host molecules obtained by enzymatic degradation of starch. All groups polar (hydroxyl OH) are located outside; all delimits a cavity having a hydrophobic character. This character allows cyclodextrins to include in their cavity, molecules hydrophobic to form inclusion complexes soluble in water (Figure 1). The three dimensional structure of β-cyclodextrin was obtained from the study of monocrystals by X-ray diffraction (and even a few monocrystals cyclodextrin complexes invited) which helped to highlight the structure truncated of cyclodextrins and to determine the dimensions of the cavities of each of these (Saenger, 1998) (Figure 2 and Figure 3). IGI GLOBAL PROOF International Journal of Chemoinformatics and Chemical Engineering, 4(1), 19-36, January-June 2013 21 Copyright © 2013, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited. Triphenylphosphine and its Derivatives Triphenylphosphine is a phosphoric resin used in formation reactions of Ether, in organic synthesis and also in the necrophagous of alkaloids. Triphenylphosphine and its derivatives are also used in the pharmaceutical industry because they have the ability to include in environments called active sites. These molecules play a major role in the inclusion field and are often used as guest molecules. These molecules are called triphenylphosphines given the presence of three phenyls and one phosphorus bound with them. We will show this molecule in two dimensions in Figure 4 and Figure 5. Inclusions and Complexations Cyclodextrins are common compounds for the inclusion of hydrophobic molecules on the condition that the size of the guest agrees to the internal dimensions of the cavity. Cyclodextrins may well include some or all guest compound, which then gives rise to the formation of Figure 1. Cyclodextrins form Figure 2. Three-dimensional structure of β-cyclodextrin Figure 3. Cyclic structure of β-cyclodextrin IGI GLOBAL PROOF 22 International Journal of Chemoinformatics and Chemical Engineering, 4(1), 19-36, January-June 2013 Copyright © 2013, IGI Global. Copying or distributing in print or electronic forms without written permission of IGI Global is prohibited. complex containing possibly several (1 or 2) of cyclodextrins or guest molecules. Many examples of host-guest complexes with various structural arrangements are well described in the literature. The main structures of complexes that have been published are shown in Figure 6. The various structures of cyclodextringuest complexes in aqueous solution, described in the literature are as follows 1. Full inclusion 2. Inclusion “axial” 3. Partial inclusion 4. 2:1 complex 5. 1:2 complex 6. 2:2 complex 7. Complex “nonspecific”