Resumen de Functional gels as microreactors
- español
Hidrogelantes funcionalizados sobre autoensamblaje pueden demostrar como la catálisis enzimática mejorada basada en varios factores tales como bolsillos hidrofóbicos, cambio en pH, cambio en pKa, aumento en la concentración local de los sitios activos etc. Aquí presentamos tales tipos de hidrogelantes que son capaces de demostrar varios tipos de reacciones importantes como aldolica, Mannicli, hidrolisis, deactetalisation, etc.
- English
Low molecular weight hydrogelators appended with catalytic groups are known to show enhanced catalytic activities. These self-assembling catalytic molecules demonstrate better catalytic efficacy when compared to their analogues which are unable to aggregate. The enhanced activity has been correlated with several properties such as cooperativity, increased acidity/basicity, pKa shifts, hydrophobic pockets, etc. that come in to play upon aggregation of these molecules.
Based on the previous reports of histidine incorporated molecules we have synthesized ImVal8, a metal free low molecular gelator which was able to hydrolyze the model ester para nitro phenyl acetate demonstrating enzyme like catalysis following Michaelis-Menten model. The hydrolysis could be carried out at pHs ranging from 6 to 8. At lower pHs 6 and 6.5 high catalytic activity was recorded which could be linked to the cooperation of protonated and deprotonated imidazole groups work together. The enhanced catalytic activity also allowed the hydrogelator to hydrolyze L- and D-phenylalanine methyl ester into corresponding amino acids at physiological pH. On the other hand a soluble analogue Im8 was able to hydrolise the pNPA ester but at a considerably lower rate and no binding phenomenon was seen. This further proved the role of self-aggregation to achieve high catalytic activity.
As seen in Chapter 3 and various other reports have so far been about using either one catalytic hydrogelator or more hydrogelators working together in cooperation to perform a single reaction. The hydrogelators when mixed together have an inclination of co-assembling rather than self-sorting. We have taken advantage of the structural dissimilarity of two hydrogelators for their orthogonal assembly. These hydrogelators ProValDoc and SucVal8 were appended with mutually incompatible groups namely proline and acid group respectively. Thanks to the self-sorting, the two functional groups were spatially separated and thus were utilized to perform tandem reaction in one pot. SucVal8 was able to deprotect benzaldimethyl acetaldehyde into benzaldehyde which was used by ProValDoc to perform aldol reaction with cyclohexanone in the same pot giving the final aldol adduct in high yield and enantiomeric ratio. Whereas ProVal8 another bolaamphilic gelator with proline group structurally similar to SucVal8 when used together with SucVal8 showed a co-assembling tendency and no final aldol product was achieved in this case. Proline and acid group in this case formed a salt bridge neutralizing each other rendering them catalytically inactive.
This idea of orthogonal assembly to achieve tandem reactions was extended to a more complex reaction system-Mannich reaction. Mannich reaction is known to be catalyzed by both acidic and proline functional units. In case of acidic catalysis the reported diastreoselectivity and enantiomeric ratio have always been below par even though the reaction rates are on the higher sides. Whereas proline molecules can give high diastreo and enantioselectivity but at lower reaction rates and come with a disadvantage of using toxic organic solvents due to their low solubility. Both SucVal8 and ProValDoc were able to catalyze direct three component Mannich reaction between aniline, benzaldehyde and cyclohexanone. SucVal8 as catalyst showed very poor streoselectivity. Whereas ProValDoc showed considerably higher diastreoselectivity and enantiomeric ratio. When both the gelators were mixed the final selectivity was intermediate but considerably higher than SucVal8 alone. Knowing this we used these hydrogelators to a more complex reaction system in which benzaldehyde was replaced by benzaldehyde dimethyl acetal. We wanted to form a complex cascade-tandem system using SucVal8 and ProValDoc. We expected SucVal8 to perform deacetalisation to give benzaldehyde and subsequently perform the next step of Mannich reaction. But since the selectivity of SucVal8 for the final Mannich reaction is not good we expected that presence of ProValDoc will assist in getting higher streo and enantiomeric ratio. In the end we were able to attain to final diastreomeric ratio of anti:syn (75:25) for the mixture of ProValDoc and SucVal8 for the cascade-tandem system while SucVal8 alone showed a diastreoselctivity of 66:34 (anti:syn).
The use of catalysts for on demand control of supramolecular organization in ubiquitous in nature. Inspired by a previous report where different amounts of enzymes where used to catalytically control the supramolecular organization of dipeptide gelators we decide to check one of the catalytic gelators for the same. SucVal8 was used to control the formation and subsequent self-assembly of a new hydrogelator 16 based on the formation of hydrazone catalyzed by SucVal8 between the precursors 14 and 15. Use of various concentrations of SucVal8 allowed to have a control over the rate of formation of 16 and thus allowed to fine tune the kinetic of the self-assembly. Thus we were able to attain a double network system of SucVal8 and 16 in the same pot. The kinetics of formation of 16 allowed to have the final double network hydrogelator of varying storage modulus. Higher rate of formation resulted in increased rate of self-assembly of 16 giving a kinetically trapped mechanically stronger double network gel system.
