Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

Ilija N. Cvijetić, Tatjana Ž. Verbić, Branko J. Drakulić, Dalibor M. Stanković, Ivan O. Juranić, Dragan D. Manojlović, Mire Zloh

Abstract


Redox properties of a set of aryldiketo acids (ADKs), small organic molecules that comprise 2,4-dioxobutanoic acid moiety, were studied. Along with well-known HIV-1 integrase (IN) inhibition, ADKs exert widespread biological activities. The aim of this work was to evaluate effects of aryl substitutions on properties of dioxobutanoic moiety that is involved in key interactions with metal ions within active sites of target enzymes. The effect of pH on electronic properties of nine congeners was examined using cyclic voltammetry and differential pulse polarography. Compounds were chosen as a simple set of congeners, bearing Me-groups on phenyl ring which should not be involved in electrochemical reactions, leaving diketo moiety as sole electrophore. Substitution pattern was systematically varied, yielding a set having different torsion between phenyl ring and aryl keto group (Ar-C(O)). Protonation state of ADKs at different pH values was determined from experimentally obtained pKas. The results showed that the equal number of protons and electrons is involved in the oxidation and reduction reactions at the surface of electrode. Quantitative linear correlations between reduction potentials and energies of frontier orbitals, calculated for neutral, monoanionic and corresponding radical anionic species, and steric parameter were found.

Keywords


aryldiketo acids (ADKs); redox properties; structure–property relationship; acidity constants.

Full Text:

PDF (5,388 kB)

References


D. J. Hazuda, P. Felock, M. Witmer, A. Wolfe, K. Stillmock, J. A. Grobler, A. Espeseth, L. Gabryelski, W. Schleif, C. Blau, M. D. Miller, Science 287 (2000) 646

J. S. Wai, M. S. Egbertson, L. S. Payne, T. E. Fisher, M. W. Embrey, L. O. Tran, J. Y. Melamed, H. M. Langford, Guare James P., L. Zhuang, V. E. Grey, J. P. Vacca, M. K. Holloway, A. M. Naylor-Olsen, D. J. Hazuda, P. J. Felock, A. L. Wolfe, K. A. Stillmock, W. A. Schleif, L. J. Gabryelski, S. D. Young, J. Med. Chem. 43 (2000) 4923

J. J. Tan, C. Liu, H. X. Sun, J. X. Cong, M. L. Hu, X. C. Wang, J. X. Liang, Mini Rev. Med. Chem. 12 (2012) 875

G. Cuzzucoli Crucitti, M. Métifiot, L. Pescatori, A. Messore, V. N. Madia, G. Pupo, F. Saccoliti, L. Scipione, S. Tortorella, F. Esposito, A. Corona, M. Cadeddu, C. Marchand, Y. Pommier, E. Tramontano, R. Costi, R. Di Santo, J. Med. Chem. 58 (2015) 1915

W. Zhu, Y. Zhang, W. Sinko, M. E. Hensler, J. Olson, K. J. Molohon, S. Lindert, R. Cao, K. Li, K. Wang, Y. Wang, Y.-L. Liu, A. Sankovsky, C. A. F. de Oliveira, D. a Mitchell, V. Nizet, J.A. McCammon, E. Oldfield, Proc. Natl. Acad. Sci. U. S. A. 110 (2013) 123

I. V. Krieger, J. S. Freundlich, V. B. Gawandi, J. P. Roberts, V. B. Gawandi, Q. Sun, J. L. Owen, M. T. Fraile, S. I. Huss, J.-L. Lavandera, T. R. Ioerger, J. C. Sacchettini, Chem. Biol. 19 (2012) 1556

J. Reguera, F. Weber, S. Cusack, PLoS Pathog. 6 (2010) e1001101

R. M. DuBois, P. J. Slavish, B. M. Baughman, M.-K. Yun, J. Bao, R. J. Webby, T. R. Webb, S. W. White, PLoS Pathog. 8 (2012) e1002830

K. E. B. Parkes, P. Ermert, J. Fässler, J. Ives, J. A. Martin, J. H. Merrett, D. Obrecht, G. Williams, K. Klumpp, J. Med. Chem. 46 (2003) 1153

J. Tomassini, H. Selnick, M. E. Davies, M. E. Armstrong, J. Baldwin, M. Bourgeois, J. Hastings, D. Hazuda, J. Lewis, W. McClements, Antimicrob. Agents Chemother. 38 (1994) 2827

C. Lee, J. M. Lee, N.-R. Lee, B.-S. Jin, K.J. Jang, D.-E. Kim, Y.-J. Jeong, Y. Chong, Bioorg. Med. Chem. Lett. 19 (2009) 1636

S. Liu, L.-F. Zeng, L. Wu, X. Yu, T. Xue, A. M. Gunawan, Y.-Q. Long, Z.-Y. Zhang, J. Am. Chem. Soc. 130 (2008) 17075

R. Braga, L. Hecquet, C. Blonski, Bioorg. Med. Chem.12 (2004) 2965

V. Summa, A. Petrocchi, P. Pace, V. G. Matassa, R. De Francesco, S. Altamura, L. Tomei, U. Koch, P. Neuner, J. Med. Chem. 47 (2004) 14

L. De Luca, M. L. Barreca, S. Ferro, F. Christ, N. Iraci, R. Gitto, A. M. Monforte, Z. Debyser, A. Chimirri, ChemMedChem 4 (2009) 1311

B. J. Drakulić, M. Stavri, S. Gibbons, Ž. S. Žižak, T. Ž. Verbić, I. O. Juranić, M. Zloh, ChemMedChem 4 (2009) 1971

T. Ž. Verbić, B. J. Drakulić, M. F. Zloh, J. R. Pecelj, G. V. Popović, I. O. Juranić, J. Serb. Chem. Soc. 72 (2007) 1201

T. Ž. Verbić, B. J. Drakulić, M. Zloh, I. O. Juranić, Lett. Org. Chem. 5 (2008) 692

A. Kuhn, K. G. von Eschwege, J. Conradie, Electrochim. Acta 56 (2011) 6211

K. C. Kemp, E. Fourie, J. Conradie, J. C. Swarts, Organometallics 27 (2008) 353

W. C. (Ina) du Plessis, J. J. C. Erasmus, G. J. Lamprecht, J. Conradie, T. S. Cameron, M. A. S. Aquino, J. C. Swarts, Can. J. Chem. 77 (1999) 378

M. M. Conradie, A. J. Muller, J. Conradie, S. Afr. J. Chem. 14 (2008) 13

G. S. Posyagin, E. Y. Posyagina, V. V Zalesov, S. S. Kataev, Russ. J. Gen. Chem. 71 (2001) 1574

L. Brecker, M. Pogorevc, H. Griengl, W. Steiner, T. Kappe, D. W. Ribbons, New J. Chem. 23 (1999) 437

M. Huang, W. G. Richards, G. H. Grant, J. Phys. Chem. A 109 (2005) 5198

T. Ž. Verbić, M. F. Zloh, D. M. Stanković, M. M. Sentić, D. D. Manojlović, I. O. Juranić, Keto-enol tautomerism of aryldiketo acids in aqueous solution: NMR spectroscopy and cyclic voltammetry study, in Proceedings of the 49th Meeting of the Serbian Chemical Society, Kragujevac, Serbia, 2011, p. 16

E. P. Serjeant, A. Albert, The Determination of Ionization Constants: A Laboratory Manual, 2nd ed., Chapman and Hall, London, 1971, p. 44

Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford CT, 2013

O. A. Sof’ina, N. M. Igidov, E. N. Koz’minykh, N. N. Trapeznikova, Y. S. Kasatkina, V. O. Koz’minykh, Russ. J. Org. Chem. 37 (2001) 1017

H. Beiginejad, D. Nematollahi, M. Noroozi, S. Lotfi, J. Iran. Chem. Soc. 12 (2015) 325

A. Y. Tesio, S. N. Robledo, H. Fernández, M. A. Zon, Bioelectrochemistry 91 (2013) 62

E. Gunić, I. Tabaković, K. M. Gaši, D. Miljković, I. Juranić, J. Org. Chem. 59 (1994) 1264.




DOI: http://dx.doi.org/10.2298/JSC161118021C

Refbacks

  • There are currently no refbacks.


Copyright (c) 2017 J. Serb. Chem. Soc.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IMPACT FACTOR 0.970 (120 of 163 journals)
5 Year Impact Factor 0.997 (111 of 163 journals)