Electrochemical Properties of Biologically Active Heterocyclic Naphthoquinones

Journal of the Brazilian Chemical Society

Azevedo, Dayse C.¹  Zani, Carlos L.¹  Universidade Federal de Minas Gerais, Belo Horizonte, Brazil¹  Oliveira, Alaíde B. de¹  Tonholo, Josealdo¹  Universidade de São Paulo, Brazli¹  Goulart, Marília O. F.¹  Freitas, Luciano R.¹  Abreu, Fabiane C. de¹  Centro de Pesquisas René Rachou/ FIOCRUZ, Belo Horizonte, Brazil¹  Universidade Federal de Alagoas, Maceió, Brazil¹ 

关键词: cyclic voltammetry;    quinone reduction;    heterocyclic naphthoquinones;    substituent effects;    biological activities;   

DOI  :  10.1590/S0103-50531998000200008

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

Several natural and synthetic heterocyclic naphthoquinones have important biological activities such as antitumoral, anti-protozoan and antibiotic1-9. In cancer chemotherapy, they are considered the second more important group8. After an initial bioreduction step, their mode of action normally involves the generation of active oxygen species by redox cycling8, intercalation in the DNA double helix10 or alkylation of biomolecules11. As the bioreduction of quinones is influenced by their redox properties, the understanding of how structural features of the quinones are related to these properties is an important step to comprehend their mechanism of action and predict modifications to improve their biological activity12. A plethora of quinones is known, the electrochemistry of which has been widely studied13,14. There are, however, few reports on electrochemical studies of heterocyclic naphthoquinones1,13-16. Recently, we observed a contribution of the easiness of reduction on the trypanocidal activity of seventeen synthetic and natural naphthoquinones17. Correlation between antimalarial activities and redox potential was earlier observed9. As the electrochemistry of these quinones have not yet been published, we report here their electrochemical parameters, including Epc and E1/2 values of for their cathodic waves, in aprotic medium, along with results from electrolyses for some of them. We also compare antimalarial activities and electrochemical data. The aprotic medium was chosen because it mimics the hydrophobic cell environment18.   Experimental Chemicals The naphthofuranquinones (NFQ), naphthothiophenquinones (NTQ), naphthodihydropyranquinones (NDQ) used in this work were described elsewhere (1-619, 7-1220, 13-1419 and 15-1721-22). Solvents, electrolytes and solutions N,N-Dimethylformamide (Merck, Uvasol Grade) was treated with cupric sulfate, filtered and distilled at reduced pressure through a glass Vigreux column (12 cm). Tetra-n-butylammonium perchlorate (TBAP) was prepared from the corresponding bromide (Aldrich or Lancaster Synthesis) and perchloric acid 70% (Aldrich). The resulting salt was washed with cold water until neutral pH, recrystallized from ethyl acetate and thoroughly dried before use (2 days, 70 °C, under high vacuum). Test solutions of the quinones (1 mM) were prepared just before electrochemical experiments and the dissolved oxygen eliminated by bubbling the solution with dry nitrogen. During the experiments the cell was covered with aluminum foil to minimize photoreactions. Electrochemical Measurements Cyclic voltammetry (CV) was performed using a PAR model 273 A/PAR EG & G potentiostat/galvanostat equipped with an HP 7090A measuring plotter system. The whole system was controlled by a 386 SX/Microtec compatible PC. A SMDE 303 A/EG & G PARC hanging mercury electrode (area 0.009664 cm2) was used as the working electrode, together with a platinum counter-electrode and a home-built Ag/AgCl/NaCl (0.1 M) Luggin reference electrode, isolated from the solution by a Vycor rod. The scan rate was in the range 0.035 - 35 V s-1. Reduction 2, 3, 7 and 14, were electrolyzed at a potentiostat-galvanostat 371/PAR EG&G. The current was integrated electronically. Conventional glass cells were used with the anode and cathode compartments separated by medium porosity sintered glass. The electrolyte was pre-electrolyzed at -2.0 V until the background current reached a low steady value. The following description is typical for electrolyses procedures and methods for work-up and isolation of products. 2-Methylfuran-para-naphthoquinone, 2 (0.0175 g, 0.08 mmol), dissolved in 40 mL of DMF/TBAP (0.1M) was electrolyzed at an Hg pool cathode held at -0.9 V. After consumption of 1 F/mol, the cell current reached residual current. The potential was then increased to the potential of the second wave (-1.6 V). After uptake of an additional 1 F/mol, the cell current was still 50% of the initial one. The decrease of the current turned very slow, and the electrolysis was finished. Addition of water, followed by ether extraction furnished a colorless compound that immediately suffered air oxidation to give back the original quinone. The electrolysis was then, carried out, using quinones 3 (0. O146 g, 0.065 mmol)/7 (0.0216 g, 0.101 mmol) and 14 (0.0205 g, 0.086 mmol) in the presence of freshly distilled acetic anhydride (5 mL) as an electrophile, close to the potential of the second wave (-1.7 V). After reaching the residual current, with exact consumption of 2 F/mol, the acetylated compounds 18, 19 and 20 were obtained, with yields of 100%, 82%, and 94%, respectively. 4,9-Diacetoxy-2-ethylnaphtho[2,3-b]furan (18) Colorless crystals, m.p. 165-167 °C (CHCl3); IR KBr/max(cm-1):1762 (nCO), 1600 (n arom. ring), 1366 (dOCOC),1203, 1164, 1042 (dCO), 765, 735 (n furan). 1H-NMR (CDCl3, 400 MHz, d): 1.36 (t, J = 7.5 Hz, 3H, CH2CH3), 2.52 (s, 3H, COCH3), 2.57 (s, 3H, COCH3), 2.82 (dq, J = 7.5 Hz, J = 1.0 Hz, 2 H, CH2CH3), 6.38 (t, J = 1.0 Hz, 1H, furan ring), 7.42-7.52 (m, 2 H, arom. ring) 7.90-7.95 (m, 2H, arom. ring). 13C-NMR (CDCl3, d): 11.3 (Me), 20.6 (Me), 20.8 (Me), 22.0 (CH2), 98.6 (CH), 120.9 (CH), 121.0 (CH), 123.5 (Cq), 123.6 (Cq), 124.4 (Cq), 124.7 (CH), 125.3 (CH), 126.2 (Cq), 134.5 (Cq), 144.3 (Cq), 164.4 (Cq), 168.3 (CO), 168.8 (CO). 4,9-Diacetoxynaphtho[2,3-b]thiophen (19) Colorless crystals, m.p. 237 °C IR KBr/max(cm-1):1752, 1365, 1206, 1163, 1069, 1014, 758. 1H-NMR (CDCl3, 400 MHz, d): 2.56 (s, 6H, COCH3), 7.28 (bs, 1H, thiophen ring), 7.46 (bs, 1H, thiophen ring), 7.52-7.55 (m, 2H, arom. ring), 7.85-7.89 (m, 1H, arom. ring), 7.93-7.97 (m, 1H, arom. ring).13C-NMR (CDCl3, d): 20.7 (Me), 20.7 (Me), 120.2 (CH), 120.6 (CH), 121.6 (CH), 124.5 (Cq), 124.8 (Cq), 125.9 (CH), 126.2 (CH), 128.8 (CH), 130.9 (Cq), 131.9 Cq), 138.4 (Cq), 138.6 (Cq), 168.2 (CO), 169.0 (CO). 4,5-Diacetoxynaphtho[1,2-b]furan (20) Colorless crystals, m.p. 134-136 °C. IR KBr/max(cm-1): 1766, 1369, 1206, 1042, 1010, 764, 721. 1H-NMR (CDCl3, 400 MHz, d): 1.39 (d, J = 7.1 Hz, 6H, CH(CH3)2), 2.41 (s, 3H, COCH3), 2.46 (s, 3H, COCH3), 3.17(m, 1H, CHCH3)2), 6.38 (s, 1H, furan ring), 7.4-7.51 (m, 1H, arom. ring), 7.53-7.59 51 (m, 1H, arom. ring), 7.84 (d, J = 8.1 Hz, 1H, arom. ring), 8.26 (d, J = 8.1 Hz, 1H, arom. ring). 13C-NMR (CDCl3, d): 20.4 (Me), 20.6 (Me), 21.0 (2 x Me), 28.4 (CH), 98.9 (CH), 119.3 (Cq), 119.8 (Cq), 120.2 (CH), 121.9 (CH), 124.4 (CH), 125.5 (CH), 126.3 (CH), 132.8 (Cq), 133.3 (Cq), 148.2 (Cq), 165.0 (Cq), 167.9 (CO), 168.6 (CO).   Results and Discussions The cyclic voltammograms of the naphthoquinones in DMF showed two typical waves corresponding to two sequential reversible or quasi-reversible one-electron transfer processes13,14. The first wave was related to the redox couple quinone (Q) / semiquinone anion radical (Q·) and the second wave due to the semiquinone anion radical (Q·) / quinone dianion (Q2-). The electrochemical parameters (Epc1 and Epc2, Epa1 and Epa2, E(1/2)1 and E(1/2)2, DEpc, for both waves, and Epc2-Epc1), for seventeen heterocyclic naphthoquinones (Fig. 1) were measured from cyclic voltammograms registered with a scan rate of 0.100 V s-1. These data are listed in Table 1.     The Epc1 of the para-naphthoquinone derivatives 1-12 is in the range -0.76 V 0.87 V while Epc2 varies from -1.40 V to -1.48 V (Fig. 2). In the

【 授权许可】

Unknown