Glutathione (GSH) is a common antioxidant and its biological activity depends on the conformation and protonation state. We used molecular dynamics, Raman and Raman optical activity (ROA) spectroscopies to investigate GSH structural changes in a broad pH range. Factor analysis of the spectra provided protonation constants (2.05, 3.45, 8.62, 9.41) in good agreement with previously published values. Following the analysis, spectra of differently protonated forms were obtained by extrapolation. The complete deprotonation of the thiol group above pH 11 was clearly visible in the spectra; however, many spectral features did not change much with pH. Experimental spectra at various pH values were decomposed into the simulated ones, which allowed us to study the conformer populations and quality of molecular dynamics (MD). According to this combined ROA/MD analysis conformation of the GSH backbone is affected by the pH changes only in a limited way. The combination of ROA with the computations thus has the potential to improve the MD force field and obtain more accurate populations of the conformer species. The methodology can be used for any molecule, but for a more detailed insight better computational techniques are needed in the future.

Department of Analytical Chemistry Faculty of Chemical Engineering University of Chemistry and Technology Technická 5 16628 Prague 6 Czech Republic

Department of Optics Palacký University 17 listopadu 12 77146 Olomouc Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo náměstí 2 16610 Prague 6 Czech Republic

Zobrazit více v PubMed

T. Ziglari, A. Allameh, Aflatoxins - Recent Advances and Future Prospects (Ed.: M. Razzaghi-Abyaneh), IntechOpen, Iran 2013, pp. 267-286;

S. L. Nuttall, U. Martin, A. J. Sinclair, M. J. Kendall, Lancet 1998, 351, 645-645;

S. C. De Rosa, M. D. Zaretsky, J. G. Dubs, M. Roederer, M. Anderson, A. Green, D. Mitra, N. Watanabe, H. Nakamura, I. Tjioe, Eur. J. Clin. Invest. 2000, 30, 915-929;

R. L. Woltjer, W. Nghiem, I. Maezawa, D. Milatovic, T. Vaisar, K. S. Montine, T. J. Montine, J. Neurochem. 2005, 93, 1047-1056;

Z. Ke, Z. Yu, Q. Huang, Plasma Processes Polym. 2013, 10, 181-188.

H. J. Forman, H. Zhang, A. Rinna, Mol. Aspects Med. 2009, 30, 1-12;

G. M. A. Cançado, V. E. De Rosa, J. H. Fernandez, L. G. Maron, R. A. Jorge, M. Menossi, Funct. Plant Biol. 2005, 32, 1045-1055;

C. H. Foyer, H. Lopez-Delgado, J. F. Dat, I. M. Scott, Physiol. Plant. 1997, 100, 241-254;

D. Gangopadhyay, M. Das, K. K. Singh, P. Sharma, R. K. Singh, P. Tandon, J. Phys. Chem. B 2018, 122, 10306-10314;

P. Moldéus, I. A. Cotgreave, Methods Enzymol. 1994, 234, 482-492;

L. Sjöberg, T. E. Eriksen, L. Revesz, Radiat. Res. 1982, 89, 255-263;

S. P. Mezyk, J. Phys. Chem. 1996, 100, 8861-8866.

D. P. Dixon, I. Cummins, D. J. Cole, R. Edwards, Curr. Opin. Plant Biol. 1998, 1, 258-266;

M. Tamba, A. Torreggiani, Res. Chem. Intermed. 2002, 28, 57-70.

R. B. Martin, S. Lowey, E. L. Elson, J. T. Edsall, J. Am. Chem. Soc. 1959, 81, 5089-5095.

J. Hudecová, J. Kapitán, M. Dračínský, P. Michal, V. Profant, P. Bouř, Chem. Eur. J. 2022, 28, e202202045;

D. Gangopadhyay, P. Sharma, S. K. Singh, P. Singh, N. Tarcea, V. Deckert, J. Popp, R. K. Singh, Chem. Phys. Lett. 2015, 618, 225-230;

P. Sharma, D. Gangopadhyay, P. Singh, P. C. Mishra, V. Deckert, J. Popp, R. K. Singh, Chem. Phys. Lett. 2014, 613, 127-132;

D. Gangopadhyay, P. Sharma, R. Nandi, M. Das, S. Ghosh, R. K. Singh, RSC Adv. 2016, 6, 112562-112567;

D. Gangopadhyay, P. Sharma, S. K. Singh, P. Singh, V. Deckert, J. Popp, R. K. Singh, RSC Adv. 2016, 6, 58943-58949.

E. W. Blanch, L. Hecht, L. D. Barron, Methods 2003, 29, 196-209.

J. R. Cheeseman, M. S. Shaik, P. L. A. Popelier, E. W. Blanch, J. Am. Chem. Soc. 2011, 133, 4991-4997;

Z. Q. Wen, L. D. Barron, L. Hecht, J. Am. Chem. Soc. 1993, 115, 285-292;

V. Palivec, V. Kopecký, P. Jungwirth, P. Bouř, J. Kaminský, H. Martinez-Seara, Phys. Chem. Chem. Phys. 2020, 22, 1983-1993.

S. Yamamoto, M. Straka, H. Watarai, P. Bouř, Phys. Chem. Chem. Phys. 2010, 12, 11021-11032;

K. J. Jalkanen, R. M. Nieminen, M. Knapp-Mohammady, S. Suhai, Int. J. Quantum Chem. 2003, 92, 239-259;

A. S. Perera, J. Cheramy, C. Merten, J. Thomas, Y. J. Xu, ChemPhysChem 2018, 19, 2234-2242;

J. Jungwirth, J. Šebestík, M. Šafařík, J. Kapitán, P. Bouř, J. Phys. Chem. B 2017, 121, 8956-8964.

S. Luber, M. Reiher, J. Phys. Chem. B 2010, 114, 1057-1063;

C. Mensch, C. Johannessen, ChemPhysChem 2018, 19, 3134-3143;

I. H. McColl, E. W. Blanch, L. Hecht, L. D. Barron, J. Am. Chem. Soc. 2004, 126, 8181-8188;

J. Kessler, J. Kapitán, P. Bouř, J. Phys. Chem. Lett. 2015, 6, 3314-3319;

V. Parchaňský, J. Kapitán, P. Bouř, RSC Adv. 2014, 4, 57125-57136.

L. Nafie, Vibrational optical activity: Principles and applications, Wiley, Chichester 2011.

X. Li, K. H. Hopmann, J. Hudecová, W. Stensen, J. Novotná, M. Urbanová, J. S. Svendsen, P. Bouř, K. Ruud, J. Phys. Chem. A 2012, 116, 2554-2563;

K. H. Hopmann, J. Šebestík, J. Novotná, W. Stensen, M. Urbanová, J. Svenson, J. S. Svendsen, P. Bouř, K. Ruud, J. Org. Chem. 2012, 77, 858-869.

P. Bouř, V. Sychrovský, P. Maloň, J. Hanzlíková, V. Baumruk, J. Pospíšek, M. Buděšínský, J. Phys. Chem. A 2002, 106, 7321-7327;

S. Yamamoto, J. Kaminský, P. Bouř, Anal. Chem. 2012, 84, 2440-2451;

J. R. Cheeseman, M. J. Frisch, J. Chem. Theory Comput. 2011, 7, 3323-3334;

L. N. Vidal, F. Egidi, V. Barone, C. Cappelli, J. Chem. Phys. 2015, 142, 174101.

A. Krezel, W. Bal, Bioinorg. Chem. Appl. 2004, 2, 293-305.

M. Hope, J. Šebestík, J. Kapitán, P. Bouř, J. Phys. Chem. A 2020, 124, 674-683;

P. Michal, R. Čelechovský, M. Dudka, J. Kapitán, M. Vůjtek, M. Berešová, J. Šebestík, K. Thangavel, P. Bouř, J. Phys. Chem. B 2019, 123, 2147-2156.

P. Michal, J. Kapitán, J. Kessler, P. Bouř, Phys. Chem. Chem. Phys. 2022, 24, 19722-19733.

J. L. Liu, C. L. Li, AIP Adv. 2019, 9, 015214.

M. J. York, G. R. Beilharz, P. W. Kuchel, Int. J. Pept. Protein Res. 1987, 29, 638-646;

S. Fujiwara, G. Formicka-Kozlowska, H. Kozlowski, Bull. Chem. Soc. Jpn. 1977, 50, 3131-3135;

D. L. Rabenstein, J. Am. Chem. Soc. 1973, 95, 2797-2803;

O. Lampela, A. H. Juffer, A. Rauk, J. Phys. Chem. A 2003, 107, 9208-9220;

R. Zhang, W. Wu, J. Mol. Liq. 2011, 162, 20-25.

W. Wright, Acta Crystallogr. 1958, 11, 632-642;

L. Prade, R. Huber, T. H. Manoharan, W. E. Fahl, W. Reuter, Structure 1997, 5, 1287-1295;

H. Nishimasu, R. Ishitani, K. Yamashita, C. Iwashita, A. Hirata, H. Hori, O. Nureki, Proc. Natl. Acad. Sci. USA 2009, 106, 8180-8185.

J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman, D. A. Case, J. Comput. Chem. 2004, 25, 1157-1174.

W. M. Holden, E. P. Jahrman, N. Govind, J. T. Seidler, J. Phys. Chem. A 2020, 124, 5415-5434.

J. Kapitán, V. Baumruk, V. Kopecký Jr, R. Pohl, P. Bouř, J. Am. Chem. Soc. 2006, 128, 13451-13462;

S. Yamamoto, S. Ishiro, J. Kessler, P. Bouř, Phys. Chem. Chem. Phys. 2021, 23, 26501-26509.

P. Bouř, D. Michalík, J. Kapitán, J. Chem. Phys. 2005, 122, 144501.

K. H. Hopmann, K. Ruud, M. Pecul, A. Kudelski, M. Dračínský, P. Bouř, J. Phys. Chem. B 2011, 115, 4128-4137.

V. Parchaňský, J. Kapitán, J. Kaminský, J. Šebestík, P. Bouř, J. Phys. Chem. Lett. 2013, 4, 2763-2768.

V. Schrenková, M. S. Para Kkadan, J. Kessler, J. Kapitán, P. Bouř, Phys. Chem. Chem. Phys. 2023, 25, 8198-8208.

J. Palacký, P. Mojzeš, J. Bok, J. Raman Spectrosc. 2011, 42, 1528-1539.

P. Eilers, H. Boelens, Leiden University Medical Centre report 2005.

E. R. Malinowski, Factor Analysis in Chemistry, 2 ed., Wiley, New York 1991.

M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. J. Bearpark, J. J. Heyd, E. N. Brothers, K. N. Kudin, V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman, D. J. Fox, Gaussian 16, Gaussian, Inc., Wallingford, CT 2016.

A. Becke, Phys. Rev. A 1988, 38, 3098-3100.

J. Wang, P. Cieplak, P. A. Kollman, J. Comput. Chem. 2000, 21, 1049-1074.

D. A. Pearlman, D. A. Case, J. W. Caldwell, W. S. Ross, T. E. Cheatham, S. Debolt, D. M. Ferguson, G. Seibel, P. A. Kollman, Comp. Phys. Commun. 1995, 91, 1-41.

N. Kamiya, Y. S. Watanabe, S. Ono, J. Higo, Chem. Phys. Lett. 2005, 401, 312-317.

P. Bouř, T. A. Keiderling, J. Chem. Phys. 2002, 117, 4126-4132;

J. Hudecová, K. H. Hopmann, P. Bouř, J. Phys. Chem. B 2012, 116, 336-342.

P. Bouř, Qgrad, Academy of Sciences, Prague 2006.