RESUMEN
Efficient electronic energy transfer (EET) in the newly synthesized dyads comprised of zinc porphyrin covalently linked to one, two or four numbers of boron dipyrrin (BDP) entities is investigated. Both steady-state and time-resolved emission as well as transient absorption studies revealed occurrence of efficient singlet-singlet energy transfer from BDP to zinc porphyrin with the time scale ranging between 28 and 48 ps. A decrease in time constants for energy transfer with increasing the number of BDP units is observed revealing better antenna effect of dyads bearing higher number of boron dipyrrin entities. Further, supramolecular triads to mimic the 'antenna-reaction center' functionality of photosynthetic reaction center have been successfully constructed by coordinating fulleropyrrolidine appended with an imidazole ligand to the zinc porphyrin. The structural integrity of the supramolecular triads was arrived by optical, computational and electrochemical studies. Free energy calculations revealed possibility of photoinduced electron transfer from singlet excited zinc porphyrin to fullerene, and the preliminary transient absorption studies involving pump-probe technique are supportive of occurrence of electron transfer from (1)ZnP* to fullerene in the supramolecular triads.
RESUMEN
A structure-activity relationship study was conducted in order to probe the nature of the interaction between some 3-alkyl-N-hydroxysuccinimide derivatives and human leukocyte elastase. The structural features in substituent X (structure I) that lead to the manifestation and optimization of inhibitory activity have been examined. The data suggest that the presence of an alkyl or aryl(sulfonyloxy) group in the active compounds may serve a triple purpose, namely, it functions as a good leaving group as dictated by the established mechanism of action of this class of compounds, secondly, it may enhance binding by assuming a favorable spatial orientation and, thirdly, it may increase the chemical reactivity of the carbonyl carbon in the bioactive compounds.
Asunto(s)
Elastasa de Leucocito/antagonistas & inhibidores , Leucocitos/enzimología , Elastasa Pancreática/antagonistas & inhibidores , Succinimidas/química , Fenómenos Químicos , Química Física , Cristalografía por Rayos X , Humanos , Elastasa de Leucocito/química , Espectroscopía de Resonancia Magnética , Elastasa Pancreática/química , Relación Estructura-Actividad , Succinimidas/farmacologíaRESUMEN
The inhibitory activity of a series of aryl azolides and sulfonate salts toward human leukocyte elastase is reported. Several of the compounds were found to be potent inhibitors of the enzyme. Active compounds were obtained only when the specificity group and the reactive moiety were separated by a two-carbon chain. The introduction of hydrophobic groups enhanced the inhibitory activity of these compounds, with the exception of the sulfonate salts. The nature of the leaving group had a profound effect on inhibitory activity, with compounds 23 and 26 being the most active (kobsd/[I] = 11,722 and 13,500 M-1 s-1, respectively).
Asunto(s)
Compuestos Azo/síntesis química , Leucocitos/enzimología , Elastasa Pancreática/sangre , Compuestos Azo/farmacología , Humanos , Cinética , Espectroscopía de Resonancia Magnética , Elastasa Pancreática/antagonistas & inhibidores , Compuestos de Amonio Cuaternario/síntesis química , Compuestos de Amonio Cuaternario/farmacología , Espectrofotometría Infrarroja , Relación Estructura-ActividadRESUMEN
A series of amino acid-derived sulfonate salts have been synthesized. They were found to inactivate efficiently and selectively human leukocyte elastase. The sulfonate salts of the methyl esters of L-norleucine, L-norvaline and L-valine were the most potent. The enzyme is inactivated irreversibly with concomitant release of bisulfite ion. The results demonstrate for the first time that ionic compounds can indeed function as novel inhibitors for the serine proteinases.