XIV
h
International Conference on Molecular Spectroscopy, Białka Tatrzańska 2017
297
T6: P–5
Spectroscopic study of amphotericin B copper complex
and its interactions with phospholipid monolayers
at the air–water interface
Grzegorz Czernel
1
, Marta Arczewska
1
, Arkadiusz Matwijczuk
1
, Paulina Duda
1
,
Barbara Chudzik
2
, and Mariusz Gagoś
2
1
Department of Biophysics, University of Life Sciences in Lublin, Akademicka 13, 20-950, Lublin,
Poland, e-mail: grzegorz.czernel@up.lublin.pl
2
Department of Cell Biology, Institute of Biology and Biotechnology, Maria Curie-Skłodowska
University, 20-033 Lublin, Poland
Amphotericin B (AmB) is a polyene antibiotic produced by Streptomyces nodosus, used for
more than 50 years in the treatment of acute systemic fungal infections. It has been shown that
AmB is present in aqueous solutions in the form of high molecular weight aggregates which
possess weaker fungicidal properties and increased toxicity against mammalian cells. Since this
phenomenon has emerged, methods of prevention of formation of molecular aggregates of AmB
in aqueous solutions are being sought. One such method is to form a complex of AmB with
copper(II) ions (AmB–Cu
2+
). Analysis of electron absorption spectra and circular dichroism
indicate that AmB in aqueous solutions at pH values ranging from 10.5 to 11.0 forms complexes
with Cu
2+
ions with a stoichiometry of 2:1. Spectroscopic study has also shown that the AmB–
Cu
2+
complex is stable at physiological pH. The higher bioactivity of the complex in comparison
with AmB may be related to the disaggregation process.
On the basic of Langmuir technique we investigated the surface activity of AmB and its
complex and their mutual interactions with phospholipids (PC) in the monolayers at the air–
water interface. The injection of AmB and the AmB–Cu
2+
complex into PBS buffer revealed the
significant differences in the surface activity of both formulations. The complex caused an
increase in the surface pressure of 3 mN/m compared to pure AmB. The results may indicate
much higher hydrophobicity of the complex than in case of AmB. In the model lipid system it
was observed the higher increase of the surface pressure after injection of the AmB-Cu
2+
complex then for pure AmB, under the surface of monolayer formed from PC + ergosterol
mixture. In the case of monolayer formed from PC + cholesterol mixture, both formulations of
the antibiotic showed similar level of the surface pressure increase. These results indicate a
stronger interaction of the AmB–Cu
2+
complex with the ergosterol-rich membrane compared to
pure AmB. The presented investigations may partly elucidate higher fungicidal activity of AmB
complex in vitro.
Keywords: amphotericin B copper complex; aggregation; membrane activity
Acknowledgment
This research was financed by the National Science Centre of Poland on the basis of decision no. DEC-
2012/05/B/NZ1/00037.
References
[1] M. Gagoś, G. Czernel, D. M. Kamiński, K. Kostro, Biometals. 24(5) (2011) 915.
[2] B. Chudzik, G. Czernel, A. Miaskowski , M. Gagoś, Eur. J. Pharm. Sci. 97 (2017) 9.
[3] M. Arczewska, G. Czernel, M. Gagoś, J. Phys. Chem. B 120 (2016) 11191.
XIV
h
International Conference on Molecular Spectroscopy, Białka Tatrzańska 2017
298
T6: P–6
Synthesis, spectral studies and biological evaluation of monomeric
and dimeric 2-hydroxymethylpyridine copper(II) complexes
Joanna Masternak
1
, Barbara Barszcz
1
, Maciej Hodorowicz
2
,
and Katarzyna Kazimierczuk
3
1
Institute of Chemistry, Jan Kochanowski University in Kielce, 15G Świętokrzyska Str., 25-406
Kielce, Poland, e-mail: joanna.masternak@ujk.edu.pl
2
Faculty of Chemistry, Jagiellonian University, Ingardena 3 Str., 30-060 Kraków, Poland
3
Department of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza 11/12 Str.,
80-233 Gdańsk, Poland
The coordination chemistry of copper(II) is a very active research field where the studies
comprise synthesis of new mononuclear or polynuclear complexes by taking advantage of the
structural versatility provided by N, O-donor ligands. The use of six-membered heterocyclic
compound has shown to be effective in the synthesis of discrete metal-organic assemblies with
variable nuclearities and sizes [1]. Certain complexes have shown properties important for
applications in diverse areas such as pharmaceuticals, fungicides, catalysts, gas occlusion
compounds, and solvent extraction processes. Herein, we report three new copper complexes,
[Cu
2
(2-CH
2
OHpy)
5
(2-CH
2
Opy)](ClO
4
)
3
(1), [Cu(2-CH
2
OHpy)
3
](ClO
4
)
2
(2), [Cu(2-CH
2
OHpy)
2
(H
2
O)
2
][SiF
6
] (3), which have been prepared via self-assembly method. The structure of new
complexes was fully characterized by single crystal X-ray diffraction as well as by FTIR, EPR
and UV-Vis spectroscopy. Their magnetic properties were also determined. The presence of
–OH groups in the ligand (2-CH
2
OHpy) also offers interesting possibilities for being involved as
H-donors in H-bonding interactions. As a part of our continuing research activities, we report
here a new metal-organic material stabilized by strong intermolecular hydrogen bonding.
Moreover, the attention of, bioinorganic chemists has been directed towards characterization of
new copper(II) N,O-donor complexes as functional model of the active sites in metallozymes. In
fact, it is well-documented that especially copper ion because of biological relevance, has been
shown to exhibit the ability to an effective radical scavenging activity. Thus, obtained copper(II)
complexes have also been explored as the exogenous antioxidants which could diminish the
cumulative effects of free radicals and oxidative damage.
Fig. 1. Perspective view of the molecular structure of [Cu
2
(2-CH
2
OHpy)
5
(2-CH
2
Opy)](ClO
4
)
3
.
Keywords: copper(II) complexes; N,O-donors; X-ray; EPR; IR; UV-Vis; antioxidant properties
Acknowledgment
We acknowledge financial support from the Polish Ministry of Science and Higher Education (projects no.
612415).
References
[1] J. Masternak, M. Zienkiewicz-Machnik, M. Kowalik, A. Jabłońska-Wawrzycka, P. Rogala, A. Adach,
B. Barszcz, Coordin. Chem. Rew. (2016) 242.
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