ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 5, pp. 907–910. © Pleiades Publishing, Ltd., 2020.
Synthesis and Anti-Biofilm Activity of New Ferrocene Schiff Bases
B. Tanera,*, F. Sevgib, and T. Göverc
a Department of Chemistry, Faculty of Science, Selçuk University, Konya, 42031 Turkey
b Medical Laboratory Techniques, Vocational School of Health Services, Selçuk University, Konya, 42130 Turkey
c Department of Analytical Chemistry, Faculty of Pharmacy, Selçuk University, Konya, 42250 Turkey
*e-mail: bilgetaner@gmail.com
Received March 31, 2020; revised May 3, 2020; accepted May 6, 2020
Abstract—Four new Schiff bases have been synthesized. The effectiveness of ferrocene systems in inhibiting
formation of Staphylococcus aureus biofilms is tested. One of studied ferrocene Schiff bases efficiently inhibits
formation of methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus
(MRSA) biofilms.
Keywords: ferrocene, Schiff bases, staphylococcal biofilms, antibiofilm activity
DOI: 10.1134/S1070363220050254
INTRODUCTION
without further purification. Chloroform was refluxed
with calcium hydride and distilled under atmospheric
pressure. TLC was performed on silica gel plates, and
column chromatography was carried out using silica gel
(200–300 mesh). 1H and 13C NMR spectra were measured
on a Bruker 500 MHz spectrometer in CDCl3 using TMS
as the internal reference. UV-Vis spectra were recorded
on a Shimadzu UV-1700 spectrophotometer.
Ferrocene-substituted Schiff bases demonstrate high
free radical scavenging and anticancer activities [1].
Most of ferrocene derivatives synthesized over recent
years have been investigated in terms of antitumor [2–4]
and anti-infective [3–5] properties, and there is a limited
number of papers devoted to their potential of inhibiting
bacterial biofilms [6, 7]. Biofilms are surface attached
communities of microorganisms that are embedded
in a matrix of extracellular polymeric substances and
play a significant role in supporting bacterial infections.
Formation of biofilms makes bacteria more resistant
to antibiotics and the host immune response. It is
estimated that such microorganism communities could
be responsible for about 80% of bacterial infections
[8]. So far there are no drugs clinically used that target
specifically bacterial biofilms. Therefore, the current
study has been focused on designing and testing anti-
biofilm compounds that could effectively minimize and
eradicate biofilm supported infections.
Synthesis of ferrocenecarboxaldehyde (2a). DMF
(15 mL) was added to freshly distilled POCl3 (6.44 g,
42.0 mmol) under the atmosphere of N2 and cooled down
from –5 to –10°C. The reaction mixture was stirred to the
point of its complete conversion into a glassy solid. Then
a solution of ferrocene (5.3 g, 28.0 mmol) in chloroform
(60 mL) was added dropwise, the mixture was stirred at
room temperature overnight, then poured into 100 mL
ice cold water and filtered. The filtrate was neutralized
to pH 8–9 by NaOH (10%, w/v) and then extracted with
ether. The organic extracts were washed with water
and dried over anhydrous MgSO4. After evaporation of
the solvent, the crude product was recrystallized from
n-hexane to afford pure compound 2a as a crimson
solid, yield 79%. 1H NMR spectrum, δ, ppm: 9.96 s (1H,
HC=O), 4.80 d (2H, Cp-rings), 4.61 d (2H, Cp-rings),
4.28 s (5H, Cp-rings).
Ferrocenylcarboxaldehyde is a suitable precursor in
Schiff base chemistry for which reason it has been used
in synthesis of ferrocenyl derivatives containing imine
and amine functional groups. Structures of the new
ferrocene substituted Schiff bases were supported by 1H
NMR. Electrochemical properties of all compounds were
determined by cyclic voltammetry (CV).
Synthesis of ferrocenyl Schiff bases 3a–3d. The
mixture of ferrocenecarboxaldehyde 2a (0.214 g,
1.0 mmol) with an aromatic amine (1.0 mmol) was
suspended in xylene (50 mL). Ferrocenecarboxaldehyde
dissolved completely upon stirring. Basic Al2O3
EXPERIMENTAL
Unless otherwise noted, all chemicals of analytical
grade were obtained from commercial suppliers and used
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