Structure and electronic properties of (+)-catechin: aqueous solvent effects

Journal of Molecular Modeling - Tập 20 - Trang 1-13 - 2014
Erika N. Bentz1, Alicia B. Pomilio2, Rosana M. Lobayan1,3
1Instituto de Investigaciones Científicas, Universidad de la Cuenca del Plata, Facultad de Ingeniería, Corrientes, Argentina
2Instituto de Bioquímica y Medicina Molecular [IBIMOL (ex PRALIB), UBA-CONICET], Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
3Departamento de Física, Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Corrientes, Argentina

Tóm tắt

We report a study of the structure of (+)-catechin, which belongs to the family of the flavan-3-ols—one of the five most widely distributed phenolic groups. The biological activities and pharmaceutical utility of these compounds are related to antioxidant activity due to their ability to scavenge free radicals. A breakthrough in the study of the conformational space of this compound, so far absent in the literature, is presented herein. A detailed analysis of the electronic distribution, charge delocalization effects, and stereoelectronic effects is presented following application of the theory of atoms in molecules (AIM) and natural bond orbital analysis. The stability order, and the effects of electron delocalization in the structures were analyzed in depth. The molecular electrostatic potential (MEP) was also obtained, assessing changes in the electronic distribution in aqueous solution, the effects of the solvent on the intrinsic electronic properties, and molecular geometry. The effect of the aqueous solvent on MEP was also quantified, and rationalized by charge delocalization mechanisms, relating them to structural changes and topological properties of the electronic charge density. To further analyze the effects of the aqueous solvent, as well as investigating the molecular and structural properties of these compounds in a biological environment, the polarizabilities for all conformers characterized were also calculated. All results were interpreted on the basis of our accumulated knowledge on (4α→6", 2α→O→1")-phenylflavans in previous reports, thus enriching and deepening the analysis of both types of structure.

Tài liệu tham khảo

Visioli F, Bellomo G, Galli C (1998) Free radical-scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun 247:60–64 Visioli F, Galli C (1998) Olive oil phenols and their potential effects on human health. J Agric Food Chem 46:4292–4296 Mercader AG, Pomilio AB (2012) (Iso)Flav(an)ones, chalcones, catechins, and theaflavins as anticarcinogens: mechanisms, anti-multidrug resistance and QSAR studies. Curr Med Chem 19:4324–4347 Mercader AG, Pomilio AB (2011) Biflavonoids: occurrence, structural features and bioactivity. Nova Science, New York, 978-1-62100-354-0 Mercader AG, Pomilio AB (2013) Naturally-occurring dimers of flavonoids as anticarcinogens. Anticancer Agents Med Chem 13(8):1217–1235 Harborne JB, Williams CA (2000) Advances in flavonoid research since 1992. Phytochemistry 55:481–504 Elhabiri M, Figueiredo P, Toki K, Saito N, Brouillard RA (1997) Anthocyanin–aluminium and –gallium complexes in aqueous solution. J Chem Soc Perkin Trans 2:355–362 Pérez-González A, Rebollar-Zepeda AM, León-Carmona JR, Galano A (2012) Reactivity indexes and O–H bond dissociation energies of a large series of polyphenols: implications for their free radical scavenging activity. J Mex Chem Soc 56(3):241–249 Mendoza-Wilson AM, Lardizabal-Gutiérrez D, Torres-Moye E, Fuentes-Cobas L, Balandrán-Quintana RR, Camacho-Dávila A, Quintero-Ramos A, Glossman-Mitnik D (2007) Optimized structure and thermochemical properties of flavonoids determined by the CHIH(medium) DFT model chemistry versus experimental techniques. J Mol Struct 871:114–130 Mendoza-Wilson AM, Glossman-Mitnik D (2006) Theoretical study of the molecular properties and chemical reactivity of (+)-catechin and (−)-epicatechin related to their antioxidant ability. J Mol Struct THEOCHEM 761:97–106 Zhang J, Du F, Peng B, Lu R, Gao H, Zhou Z (2010) Structure, electronic properties, and radical scavenging mechanisms of daidzein, genistein, formononetin, and biochanin A: a density functional study. J Mol Struct THEOCHEM 955:1–6 Markovic ZS, Mentus SV, Dimitric Markovic JM (2009) Electrochemical and density functional theory study on the reactivity of fisetin and its radicals: implications on in vitro antioxidant activity. J Phys Chem A 113:14170–14179 Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biol Med 7:933, and references therein Zhang HY, Wang LF, Sun YM (2003) Why B-ring is the active center for genistein to scavenge peroxyl radical: a DFT study. Bioorg Med Chem Lett 13:909–911 Antonczak S (2008) Electronic description of four flavonoids revisited by DFT method. J Mol Struct THEOCHEM 856:38–45 Leopoldini M, Russo N, Toscano M (2007) A comparative study of the antioxidant power of flavonoid catechin and its planar analogue. J Agric Food Chem 55:7944–7949 Lobayan RM, Jubert AH, Vitale MG, Pomilio AB (2009) Conformational and electronic (AIM/NBO) study of unsubstituted A-type dimeric proanthocyanidin. J Mol Model 15:537–550 Bentz EN, Jubert AH, Pomilio AB, Lobayan RM (2010) Theoretical study of Z isomers of A-type dimeric proanthocyanidins substituted with R = H, OH and OCH3: stability and reactivity properties. J Mol Model 16:1895–1909 Lobayan RM, Bentz EN, Jubert AH, Pomilio AB (2012) Structural and electronic properties of Z isomers of (4α → 6",2α → O → 1")-phenylflavans substituted with R = H, OH and OCH3 calculated in aqueous solution with PCM solvation model. J Mol Model 18:1667–1676 Lobayan RM, Bentz EN, Jubert AH, Pomilio AB (2013) Charge delocalization in Z- isomers of (4α → 6",2α → O → 1")-phenylflavans with R = H, OH and OCH3. Effects on bond dissociation enthalpies and ionization potentials. J Comput Theor Chemistry 1006:37–46 Olejniczak S, Potrzebowski MJ (2004) Solid state NMR studies and density functional theory (DFT) calculations of conformers of quercetin. Org Biomol Chem 2:2315–2322 Miertus S, Scrocco E, Tomasi J (1981) Electrostatic interaction of a solute with a continuum. A direct utilizaion of ab initio molecular potentials for the prevision of solvent effects. J Chem Phys 55:117–129 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA, Vreven T Jr, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) Gaussian 03, revision B.02. Gaussian, Pittsburgh Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789 Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652 Leopoldini M, Marino T, Russo N, Toscano M (2004) Antioxidant properties of phenolic compounds: H-atom versus electron transfer mechanism. J Phys Chem A 108:4916–4922 Zhang HY, Sun YM, Wang XL (2003) Substituent effects on O–H bond dissociation enthalpies and ionization potentials of catechols: a dft study and its implications in the rational design of phenolic antioxidants and elucidation of structure–activity relationships for flavonoid antioxidants. Chem-A Eur J 9:502–508 Bader RFW (1995) Atoms in molecules—a quantum theory. Oxford University Press, Oxford Glendening ED, Reed AE, Carpenter JE, Weinhold F NBO 3.1. Program as implemented in the Gaussian 98 package. Gaussian, Wallingford, CT Biegler-Koning FW, Bader RFW, Tang TH (1982) Calculation of the average properties of atoms in molecules II. J Comput Chem 3:317–328 Flúkiger P, Lúthi HP, Portmann S, Weber J (2000) MOLEKEL 4.0. Swiss Center for Scientific Computing, Manno Bader RFW (1990) A quantum theory of molecular structure and its applications. Chem Rev 91:893–928 Bader RFW (1998) A bond path: a universal indicator of bonded interactions. J Phys Chem A 102:7314–7323 Politzer P, Landry SJ, Warnheim T (1982) Proposed procedure for using electrostatic potentials to predict and interpret nucleophilic processes. J Phys Chem 86:4767–4771 Politzer P, Abrahmsen L, Sjoberg P (1984) Effects of amino and nitro substituents upon the electrostatic potential of an aromatic ring. J Am Chem Soc 106:855–860 Politzer P, Laurence PR, Jayasuriya K (1985) Molecular electrostatic potentials: an effective tool for the elucidation of biochemical phenomena. Environ Health Perspect 61:191–202 Roy DK, Balanarayan P, Gadre SR (2009) Signatures of molecular recognition from the topography of electrostatic potential, J. Chem Sci 121:815–821 Politzer P, Truhlar DG (eds) (1981) Chemical applications of atomic and molecular electrostatic potentials. Plenum, New York Aparicio S (2010) A systematic computacional study on flavonoids. Int J Mol Sci 11:2017–2038 Desiraju GR, Steiner T (1999) The weak hydrogen bond in structural chemistry and biology. Oxford University Press, New York Weber KC, Honório KM, Bruni AT, da Silva ABF (2006) The use of classification methods for modeling the antioxidant activity of flavonoid compounds. J Mol Model 12:915–920