The molecular mechanism of enzymatic processes induced by cytochrome P450 is of importance for biosensor applicationsi as well as for construction of biological interfaces via immobilization of enzymes in the condensed environment.ii These interfaces are known to be able to model the drug metabolism under electrochemical conditions.iii The electron exchange plays a key role in the P450 catalytic cycleiv responsible for reductive dehalogenation of environmental pollutants, including herbicides both in vivo and in electrochemical experiments.v It is worth mentioning that enzymatic active centers are hydrophobic in nature, thus containing a very few water molecules.vi Additionally, the substrate molecule is bound in the active site by weak non-covalent bonds, thus keeping its native electronic structure. Therefore, resonance dissociative electron attachment (DEA) to isolated molecules in vacuo can serve as a model of enzymatic processes under reductive conditions as shown in case of some widely used non-steroidal anti-inflammatory drugs.vii The present work reports formation of transient negative ions and their decay for the halogenated herbicides atrazine and bromoxynil studied by means of electron transmission spectroscopy (ETS) and DEA spectroscopy. Dehalogenation of atrazine and bromoxynil is found to be the dominant decay of the temporary molecular negative ions formed at very low (thermal) energies of the incoming electrons. It is concluded that formation of negative ions by electron donation in enzymatic active centers followed by their dissociation along the sigma bond can be considered as a unifying mechanism of the initial step of reductive dehalogenation catalyzed by P450 enzymes. The present findings attract attention on the role of the resonance electron attachment mechanism in electron-driven enzymatic processes. The work was supported by RFBR grants (17-03-00196 and 15-29-05786) and by the Italian Ministero dell’Istruzione, dell’Università e della Ricerca. i Bistolas, N., Wollenberger, U., Jung, C., Scheller, F. W. Biosens. Bioelectron. 2005, 20(12), 2408-2423. ii Manoli, K., Magliulo, M., Mulla, M.Y., Singh, M., Sabbatini, L., Palazzo, G., Torsi, L. Angew. Chem. Int. Ed. 2015, 54(43), 12562-12576. iii Iwuoha, E.I., Joseph, S., Zhang, Z., Smyth, M.R., Fuhr, U., de Montellano, P.R.O. J. Pharm. Biomed. Anal. 1998, 17(6), 1101-1110. iv Shumyantseva, V.V., Bulko, T.V., Archakov, A.I. J. Inorg. Biochem. 2005, 99(5), 1051-1063. v Rotko, G., Romańczyk, P.P., Andryianau, G., Kurek, S.S. Electrochem. Commun. 2014, 43, 117-120. vi Poully, J.C., Nieuwjaer, N., Schermann, J.P. Phys. Scrip. 2008, 78(5), 058123. vii Pshenichnyuk, S.A., Modelli, A. J. Chem. Phys. 2012, 136(23), 234307.
Molecular mechanism of reductive dehalogenation by P450 enzymes: possible importance of dissociative electron attachment for biosensor applications.
MODELLI, ALBERTO
2017
Abstract
The molecular mechanism of enzymatic processes induced by cytochrome P450 is of importance for biosensor applicationsi as well as for construction of biological interfaces via immobilization of enzymes in the condensed environment.ii These interfaces are known to be able to model the drug metabolism under electrochemical conditions.iii The electron exchange plays a key role in the P450 catalytic cycleiv responsible for reductive dehalogenation of environmental pollutants, including herbicides both in vivo and in electrochemical experiments.v It is worth mentioning that enzymatic active centers are hydrophobic in nature, thus containing a very few water molecules.vi Additionally, the substrate molecule is bound in the active site by weak non-covalent bonds, thus keeping its native electronic structure. Therefore, resonance dissociative electron attachment (DEA) to isolated molecules in vacuo can serve as a model of enzymatic processes under reductive conditions as shown in case of some widely used non-steroidal anti-inflammatory drugs.vii The present work reports formation of transient negative ions and their decay for the halogenated herbicides atrazine and bromoxynil studied by means of electron transmission spectroscopy (ETS) and DEA spectroscopy. Dehalogenation of atrazine and bromoxynil is found to be the dominant decay of the temporary molecular negative ions formed at very low (thermal) energies of the incoming electrons. It is concluded that formation of negative ions by electron donation in enzymatic active centers followed by their dissociation along the sigma bond can be considered as a unifying mechanism of the initial step of reductive dehalogenation catalyzed by P450 enzymes. The present findings attract attention on the role of the resonance electron attachment mechanism in electron-driven enzymatic processes. The work was supported by RFBR grants (17-03-00196 and 15-29-05786) and by the Italian Ministero dell’Istruzione, dell’Università e della Ricerca. i Bistolas, N., Wollenberger, U., Jung, C., Scheller, F. W. Biosens. Bioelectron. 2005, 20(12), 2408-2423. ii Manoli, K., Magliulo, M., Mulla, M.Y., Singh, M., Sabbatini, L., Palazzo, G., Torsi, L. Angew. Chem. Int. Ed. 2015, 54(43), 12562-12576. iii Iwuoha, E.I., Joseph, S., Zhang, Z., Smyth, M.R., Fuhr, U., de Montellano, P.R.O. J. Pharm. Biomed. Anal. 1998, 17(6), 1101-1110. iv Shumyantseva, V.V., Bulko, T.V., Archakov, A.I. J. Inorg. Biochem. 2005, 99(5), 1051-1063. v Rotko, G., Romańczyk, P.P., Andryianau, G., Kurek, S.S. Electrochem. Commun. 2014, 43, 117-120. vi Poully, J.C., Nieuwjaer, N., Schermann, J.P. Phys. Scrip. 2008, 78(5), 058123. vii Pshenichnyuk, S.A., Modelli, A. J. Chem. Phys. 2012, 136(23), 234307.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
