EPR study of anion radicals of various N-quinonyl amino acids

Abstract

Since peptide quinones possess great clinical potential in targeted chemotherapy, several series of novel N-quinonyl amino acids have been synthesized and their first products of reduction were studied by EPR spectroscopy. EPR spectra of the corresponding radical adducts were identified by computer simulation. The dependence between the splitting constants and the chemical structure of the N-quinonyl amino acids anion radicals was examined.

Synthesis and Cytotoxic Evaluation of a Series of 2-Amino-Naphthoquinones against Human Cancer Cells

“…The title compounds were obtained in an one-pot Michael nucleophilic 1,4-addition procedure (Scheme 1) from commercially available 1,4-naphthoquinone ( 1 ) and suitable α- and other amino acids or esters thereof [13,14]. Thus, compounds 2 – 11 were obtained from direct displacement with suitable amino acids or the corresponding ethyl esters in the presence of a base in polar protic or aprotic solvents at room temperature (see Experimental for details).…”

“…Obtained as an orange solid in 58% yield from L-alanine after 3 h reaction, mp 148–150°C (lit. : 139–142 °C [13]); IR (ATR) ν max /cm −1 3356, 1722, 1681, 1604, 1556, 1450, 1302; 1 H-NMR (DMSO- d 6 , 300 MHz) 13.14 (s, 1H), 7.98 (d, 1H J = 7.5 Hz), 7.91 (d, 1H J = 7.5 Hz), 7.81 (t, 1H J = 7.5 Hz), 7.72 (t, 1H J = 7.5 Hz), 7.27 (d, 1H, N-H, J = 7.5 Hz), 5.65 (s, 1H), 4.21 (quint, 1H J = 7.2 Hz), 1.45 (d, 3H J = 7.2 Hz); 13 C-NMR (DMSO- d 6 , 75 MHz) 181.7, 181.3, 173.1, 147.4, 134.9, 132.7, 132.4, 130.2, 126.0, 125.4, 100.9, 50.1, 16.7. = +14.4 (C = 0.01, DMSO).…”

“…The mixture was filtered under vacuum, acidified with 10% HCl and an amorphous orange solid filtered off in 80% yield, mp 210–212 ° C (lit. : 210–211 °C [13,26]); IR (ATR) ν max /cm −1 3335. 2717, 2637, 1694, 1671, 1618, 1595, 1296; 1 H-NMR (CDCl 3 , 300 MHz) 12.17 (sbr, 1H), 7.95 (dd, 1H J = 7.8/0.9 Hz), 7.93 (dd, 1H J = 7.9/0.9 Hz), 7.80 (m, 1H), 7.67 (m, 1H), 5.7 (s, 1H), 3.20 (q, 2H, J = 6.6 Hz), 2.30 (t, 2H, J = 7.2 Hz), 1.78 (quint, 2H, J = 7.2 Hz); 13 C-NMR (CDCl 3 , 75 MHz): 181.5, 181.3, 174.3, 148.6, 134.8, 133.2, 132.1, 130.4, 125.8, 125.3, 99.3, 41.2, 30.6, 22.6.…”

Synthesis, electrochemical and spectral properties of some ω-N-quinonyl amino acids

“…This behavior, which is similar to that found for the 1,4-naphthoquinonyl amino acids series, suggests that the glycine derivative forms also an unstable semiquinone anion-radical, which undergoes NH-CH 2 or CH 2 -CO 2 H bond cleavage, thus forming the appropriate 2-amino-1,4-naphthoquinone. EPR studies of semiquinone anion radicals of different quinonyl amino acids (Bittner et al, 2000;Rahimipour et al, 1996) proved that while the unpaired electron is equally distributed on the naphthalenic ring, its density is mainly localized on the nitrogen atom. The unstable semiquinone radical leads to spontaneous decomposition of the semiquinone via the side chain cleavage.…”

Synthesis of Amino Acid–Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines

“…In this regard, the synthesis and biological activities of some naphthoquinone–amino acids have been reported in several publications; nonetheless, all of these methodologies present different drawbacks, like low yields and/or long reaction times [19,20,21,22,23,24,25,26,27,28,29]. To our knowledge, the synthesis of naphthoquinone–amino acid derivatives has not been reported using microwave and ultrasound irradiation, which offer diverse advantages to conventional synthesis.…”