Synthesis and antimicrobial activities of phosphonium salts on basis of triphenylphosphine and 3,5-di-tert-butyl-4-hydroxybenzyl bromide

Article abstract of DOI:10.1080/10426507.2012.740694

We report the structures of two new phosphonium salts prepared via the reaction of (substituted)benzyl bromides with triphenylphosphine. The antibacterial and antifungal activities are reported.

Full text of DOI:10.1080/10426507.2012.740694

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Phosphorus, Sulfur, and Silicon and the
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Synthesis and Antimicrobial Activities
of Phosphonium Salts on Basis of
Triphenylphosphine and 3,5-Di-Tert-
Butyl-4-Hydroxybenzyl Bromide
Irina Galkina a , Yuliya Bakhtiyarova a , Vitaliy Andriyashin a ,
Vladimir Galkin a & Rafael Cherkasov a
a A. M. Butlerov Chemical Institute, Kazan Federal University ,
Kazan , Tatarstan , Russian Federation
Accepted author version posted online: 01 Nov 2012.Published
online: 08 May 2013.
To cite this article: Irina Galkina , Yuliya Bakhtiyarova , Vitaliy Andriyashin , Vladimir Galkin &
Rafael Cherkasov (2013) Synthesis and Antimicrobial Activities of Phosphonium Salts on Basis of
Triphenylphosphine and 3,5-Di-Tert-Butyl-4-Hydroxybenzyl Bromide, Phosphorus, Sulfur, and Silicon
and the Related Elements, 188:1-3, 15-18, DOI: 10.1080/10426507.2012.740694
To link to this article: http://dx.doi.org/10.1080/10426507.2012.740694
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Phosphorus, Sulfur, and Silicon, 188:15–18, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.740694
SYNTHESIS AND ANTIMICROBIAL ACTIVITIES
OF PHOSPHONIUM SALTS ON BASIS
OF TRIPHENYLPHOSPHINE
AND 3,5-DI-TERT-BUTYL-4-HYDROXYBENZYL BROMIDE
Irina Galkina, Yuliya Bakhtiyarova, Vitaliy Andriyashin,
Vladimir Galkin, and Rafael Cherkasov
A. M. Butlerov Chemical Institute, Kazan Federal University, Kazan, Tatarstan,
Russian Federation
GRAPHICAL ABSTRACT
Abstract We report the structures of two new phosphonium salts prepared via the reaction
of (substituted)benzyl bromides with triphenylphosphine. The antibacterial and antifungal
activities are reported.
Keywords Phosphonium; antibacterial; antifungal; synthesis; X-ray structure
RESULTS AND DISCUSSION
A new series of quaternary phosphonium salts 3–6 have been prepared by the reac-
tion of triphenylphosphine with 3,5-di-tert-butyl-4-hydroxybenzyl bromide 2 in order to
obtain novel compounds 5 and 6, soluble in water, for potential medical purposes. All the
synthesized compounds were screened for their antibacterial, antifungal activity (Table 1),
and the target compounds 5 and 6 for their antioxidant activity (Table 2). The structure of
1
new compounds was established from the IR, H, 31P-NMR spectra and from TG/DSC,
XRD, and elemental analysis.
Received 28 June 2012; accepted 14 October 2012.
We are most grateful to Dr. Ziyatdinova G. K. for TAC determination.
Address correspondence to Irina Galkina, A. M. Butlerov Chemical Institute, Kazan Federal University,
Kremlevskaya 29/1, Kazan, Tatarstan 420008, Russian Federation. E-mail: gal.irina.2012@yandex.ru
15

16
I. GALKINA ET AL.
Table 1 The in vitro antimicrobial activity of the synthesized salts and the control drugs (100 μg/0.1 mL)
Microorganisms, zone of inhibition, (diameter, in mm)
Staphylococcus
aureus
Escherichia
Pseudomonas
aeruginosa
Salmonella
p .B
Candida
albicans
Compounds
сoli
3
4
5
6
45
43
39
35
16
23
—
19
18
22
17
15
16
—
15
16
13.5
12
13
8
7
16
8
13
14
10
—
35
46
48
47
16.5
—
Chlorhexidine
Penicillin
Griseofulvin
—
19
Scheme 1 depicts the synthesis of different quaternary phosphonium salts (3–6) from
2,6-di-tert-butyl-4-methylphenol (ionol) 1. Compound 2 was prepared from 1 according
to reported method,1 which was then refluxed in diethyl ether with the solutions of corre-
sponding phosphines to afford products 3, 4, 5, and 6. The obtained products were filtered,
dried, and recrystallized. Both of phosphonium nitrates 5 and 6 were synthesized from
corresponding phosphonium bromides 3 and 4 by reaction with AgNO3 in 2:1 EtOH:H2O
solution. The precipitate of AgBr was isolated; filtrate was concentrated in vacuum and
gave the corresponding colorless products 5 and 6.
The molecular structure of products 5 and 6 has been confirmed by X-ray analysis
(Figures 1 and 2).
The need of new antimicrobial and antioxidant drugs is justified because more mi-
croorganisms are being resistance to the present drugs available on the market. Resistance
of pathogenic bacteria to antibiotics is rapidly becoming a major problem in the medical
community and hospital-based healthcare settings. The search for novel agents to combat
resistant bacteria has become one of the most important areas of antibacterial research
today.2
The synthesized compounds 3, 4, 5, and 6 were screened for antibacterial and antifun-
gal activity at 100 μg/0.1 mL concentrations by using the cup–plate agar diffusion method,
Table 2 Total antioxidant capacity of quaternary phosphonium salts 5 and 6
N
Compounds
TAC (kC mol−1)
275
RSD (%)
1.6
5
5
6
237 10
3.5
Control 1
Control 2
α-Tocopherol
Ascorbic acid
195
185
3
4
1.4
2.2

SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF PHOSPHONIUM SALTS
17
Scheme 1
Figure 1 Structure of 5. (Color figure available online).
and standard drugs used were chlorhexidine, penicillin, and griseofulvin. The novel synthe-
sized phosphonium salts 3–6 show maximal activity against pathogenic microorganisms.
Starting compounds 1 and 2 were not active at all. These results are reported in Table 1.
Such a high biological activity of phosphonium bromides 3–6, we explain by their
ability to be integrated into the lipid layers of biomembranes of pathogenic microflora
eventually leading to the destruction of this last. To confirm this idea, we studied the inter-
action mechanism of phosphonium salts – synthetic phosphorus analogs of biomembranes –
with natural biological membranes (lecithin) using the model of Langmuir monolayers. It
was discovered that phosphonium salts interact with lecithin, by forming a pores, and thus
deteriorating the membrane functions.3
Figure 2 Structure of 6. (Color figure available online).

18
I. GALKINA ET AL.
Determination of TAS (Total Antioxidant Activity) is based on the coulometric
titration of analyte by electrogenerated bromine. Bromine has been electrochemically
generated at a current density 5 mA cm−2 providing 100% current yield. The end-points
in amperometric titration have been measured with two polarized platinum electrodes
(ꢀE = 300 mV). TAC experiments have been carried out at ambient temperature
23 2◦C. These results are reported in Table 2.
So, it may be concluded from our results that the synthesized compounds are potent
antimicrobial agents against pathogenic bacteria and fungi.
REFERENCES
1. Starnes, W. H.; Lauff, J. J. J. Org. Chem. 1970, 35, 1978-1986.
2. Aysel, G.; Taylan, I.; Nalan, T.; Gulten, O. Turkish J. Pharm. Sci. 2005, 2, 1-10.
3. Galkina, I. V.; Melnikova, N. B.; Bakhtiyarova, Yu. V.; Stakheev, V. V.; Galkin, V. I.; Zhiltsova,
O. Ye.; Zhukova, O. V.; Egorova, S. N. Pharmaciya (Russian J. Farmacy) 2010, 3, 47-49.