Synthesis of cobaltocenium acetylsalicylate
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 9, September, 2019
1789
difference in the absorption of light (A) corresponding to the
right and left polarizations (A = AL – AR).
The structure of the compounds obtained was studied using
the equipment of the Center for the Study of the Structure of
Molecules of the INEOS RAS.
by the interaction of positively charged metallocenium
cations with negatively charged phosphate DNA fragments.
Thus, the detected effects that cause conformational
changes in DNA will help to further clarify the mechanistic
aspects of the effect of organometallic compounds on
biological targets.
References
Experimental
1. E. W. Neuse, J. Inorg. Organomet. Polym. Mater., 2005, 15, 3.
2. G. Jaouen, Bioorganometallics: Biomolecules, Labeling,
Medicine, Wiley-VCH, Weinheim, 2006, 465 p.
3. L. V. Snegur, V. N. Babin, A. A. Simenel, Yu. S. Nekrasov,
L. A. Ostrovskaya, N. S. Sergeeva, Russ. Chem. Bull., 2010,
59, 2167.
Cobaltocene was synthesized under an argon atmosphere
from freshly prepared sodium cyclopentadienide and hexa-
ammine cobalt(II) chloride ([Co(NH3)6]Cl2) in THF by
heating for 4 h.39 M.p. 173—174 С. Yield 70%. Crystalline
compound is of dark cherry color, unstable in air. The cobalto-
cene in its crystalline form can be stored for a long time under
argon at –20 С.
4. C. Ornelas, New J. Chem., 2011, 35, 1973.
5. G. Gasser, I. Ott, N. Metzler-Nolte, J. Med. Chem., 2011,
54, 3.
Cobaltocenium acetylsalicylate (1). Acetylsalicylic acid
(3.50 g, 19.0 mmol, 1.3 eq.) in THF (150 mL) were added in
portions to cobaltocene (2.85 g, 15.0 mmol, 1.0 eq.) in 30 mL
of THF in a stream of argon. Stirring was continued for 5 min.
The solution grew yellow. Then the reaction mixture was
cooled for 12 h. The precipitate was filtered, washed with THF
and left in a desiccator over CaCl2. Yield 35%. Yellow powder,
6. G. Jaouen, A. Vessières, S. Top, Chem. Soc. Rev., 2015,
44, 8802.
7. P. Pigeon, Y. Wang, S. Top, F. Najlaoui, M. C. G. Alvarez,
J. Bignon, M. J. McGlinchey, G. Jaouen, J. Med. Chem.,
2017, 60, 8358; DOI: 10.1021/acs.jmedchem.7b00743.
8. G. M. Maguene, J. Jakhlal, M. Ladyman, A. Vallin, D. A.
Ralambomanana, T. Bousquet, J. Maugein, J. Lebibi, L. Pé-
linski, Eur. J. Med. Chem., 2011, 46, 31.
9. V. N. Kulikov, R. S. Nikulin, A. N. Rodionov, E. S. Babusenko,
V. N. Babin, L. V. Kovalenko, Yu. A. Belousov, Russ. Chem.
Bull., 2017, 66, 1122; DOI: 10.1007/s11172-017-186 4-y.
10. F. A. Larik, A. Saeed, T. A. Fattah, U. Muqadar, P. A.
Channar, Appl. Organomet. Chem., 2017, 31, e3664; DOI:
10.1002/aoc.3664.
11. V. N. Babin, Yu. A. Belousov, V. I. Borisov, V. V. Gumenyuk,
Yu. S. Nekrasov, L. A. Ostrovskaya, I. K. Sviridova, N. S.
Sergeeva, A. A. Simenel, L. V. Snegur, Russ. Chem. Bull.,
2014, 63, 2405.
12. L. V. Popova, V. N. Babin, Y. A. Belousov, Y. S. Nekrasov,
A. E. Snegireva, N. P. Borodina, G. M. Shaposhnikova, O. B.
Bychenko, P. M. Raevskii, N. B. Morozova, A. I. Ilyina,
K. G. Shitkov, Appl. Organomet. Chem., 1993, 7, 85.
13. L. V. Snegur, Yu. S. Nekrasov, N. S. Sergeeva, Z. V. Zhilina,
V. V. Gumenyuk, Z. A. Starikova, A. A. Simenel, N. B. Moro-
zova, I. K. Sviridova, V. N. Babin, Appl. Organomet. Chem.,
2008, 22, 139.
1
m.p. 128—130 C. Н NMR (CDCl3), δ: 2.19 (s, 3 H, CH3);
5.63 (s, 10 H, Cc); 6.86 (t, 2 H, Ph, J = 6.8 Hz); 6.95 (d, 2 H,
Ph, J = 6.8 Hz). 13C NMR (CDCl3), δ: 17.85 (CH3); 84.76
(C5H5); 93.12 (Ph); 99.43 (Ph); 105.91 (Ph); 116.84 (Ph);
118.44 (Ph, C (2)); 133.99 (Ph, C(1)); 156.75 (COO–); 161.60
(CH3COOAr). Found (%): C, 61.91; H, 4.65; Co, 16.4.
C19H17CoO4. Calculated (%): C, 61.97; H, 4.65; Co, 16.00.
IR (KBr), /cm–1: 3127, 3108, 1701, 1638, 1586, 1487, 1458,
1415, 1364, 1253, 1141, 1114, 1094, 1011, 867, 760, 706, 652,
562 , 498, 459.
For the titration of DNA solutions, aqueous solutions of
salt 1 were prepared. High molecular weight calf thymus DNA
(Sigma, United States) was used in the work. DNA complexes
were obtained by titration of DNA solutions in saline with
small volumes of solutions of cobaltocenium 1. The concen-
tration of DNA in the complexes was 60 mg L–1
.
1
The H and 13C NMR spectra of solutions of complex 1 in
CDCl3 were recorded on a Bruker DRX-500 spectrometer (1H,
500.13 MHz; 13C, 125.76 MHz) at 30 C. Chemical shifts are
given relative to residual protons of the solvent. IR spectra were
recorded on a Bruker TEM37 FTIR-spectrophotometer. Solvents
are purified by standard procedures.
14. A. A. Simenel, G. A. Dokuchaeva, L. V. Snegur, A. N.
Rodionov, M. M. Ilyin, S. I. Zykova, L. A. Ostrovskaya, N.
V. Bluchterova, M. M. Fomina, V. A. Rikova, Appl. Organomet.
Chem., 2011, 25, 70.
Elemental analysis was performed at the Laboratory of
Microanalysis of the INEOS RAS.
15. L. V. Snegur, M. V. Lyapunova, D. D. Verina, V. V. Kachala,
A. A. Korlyukov, M. M. Ilyin, Jr., V. A. Davankov, L. A.
Ostrovskaya, N. V. Bluchterova, M. M. Fomina, V. S.
Malkov, K. V. Nevskaya, A. G. Pershina, A. A. Simenel,
J. Organomet. Chem., 2018, 871, 10; DOI. 10.1016/j.
jorganchem.2018.06.019.
16. F. Noor, A. Wüstholz, R. Kinscherf, N. Metzler-Nolte,
Angew. Chem., Int. Ed. Engl., 2005, 44, 2429; DOI: 10.1002/
anie.200462519.
17. A. Pinto, U. Hoffmans, V. Ott, G. Fricker, N. Metzler-Nolte,
ChemBioChem., 2009, 10, 1852.
18. A. Maurer, H.-B. Kraatz, N. Metzler-Nolte, Eur. J. Inorg.
Chem., 2005, 3207.
The CD spectra were obtained using an automatic SKD-2
recording dichrograph (cooperative development of the V. A.
Engelhardt Institute of Molecular Biology, Russian Academy of
Sciences and the Institute of Spectroscopy, Russian Academy of
Sciences). Intensities of the extremes of the Cotton effect in the CD
spectra were calibrated using an aqueous solution of D-10-cam-
phorsulfonic acid, based on the value of 2.2 L mol–1 cm–1
at 291 nm. The measurements were carried out in a quartz cuvette
1 cm thick at a spectral resolution of 3 nm and a scanning speed
of 35 nm min–1. The range of measurements of spectrum was
from 200 to 400 nm. The CD values in Fig. 1 are given as the