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Cationic amphiphilic calixarenes:
self-assembling in water solutions and virus-sized DNA nanoparticles
Rodik, R.V., a Jain, N., b Miroshnichenko, S.I., a Richert, L., b Kalchenko, V.I., a Mely,
Y., b Klymchenko, A. S. b
a Institute of Organic Chemistry National Academy of Sciences of Ukraine;
Murmanska str.,5 02660, Kyiv-94, Ukraine E-mail: manli@ioch.kiev.ua
b Laboratory of Biophotonics and Pharmacology, Faculty of Pharmacy, University
of Strasbourg; 74, route du Rhin BP 60024 F-67401 Illkirch Cedex, France
E-mail: aklymchenko@pharma.u-strasbg.fr
The highly diverse biomedical applications of calixarene now include antibacterial,
anticancer, antiviral, selective enzyme blocking and mimicking, as well as protein
complexation 1 . On the other hand macro cycles (including calixarenes) were recently
used as scaffolds for the synthesis cationic agents for gene delivery. However, only a
few reports describe the interaction of cationic calix[4]arenes with DNA for gene
delivery applications 2 .
In this report, we present synthesis of cationic calixarenes and investigation of their
self-assembly in aqueous solutions. Moreover, DNA binding experiments were carried
out and good gene transfection properties of calixarenes were evidenced.
Cl
+
N
N+ N +
N +
OH
OHCl HO
HO
Cl
Cl
O O O O
1 2 2
R R R R
1
CX3 1 R= 2 R= C3 H 7 -n
CX6 1 R= 2 R=C 6 H 13 -n
CX8 1 R= 2 R=C 8 H 17 -n
CX12-8 1 R= C 12 H 25 -n, 2 R= C 8 H 17 -n
CX12 1 R= 2 R=C 12 H 25 -n
CX16 1 R= 2 R=C 16 H 33 -n
Cl
Cl Cl
O O O O
1 2 2
R R 1 R R
Cl
Cl
NH2 H N
NH2
2 H2N
Cl +
+ + Cl
N N Cl +
N
N
O O O O
1 2 2 1
R R R R
CX8N 1R= 2R=C8H17-n CX12-8N 1R= C12H25-n, 2R= C8H17-n We show that calix[4]arenes bearing long alkyl chains can form micelles of 6-9 nm
diameter at micromole concentration range, which can further condense different types
of DNA into small and stable particles of 40-100 nm diameter. These nano-particles,
which probably contain a single DNA molecule, exhibit promising transfection
properties in cell culture 3 .
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N+ N +
N +
Cl OH
Cl OH
HO
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O O O O
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a b c d
a: chemical structure of CX8; b: its schematic view; c: nanoscopic micelle formation
in aqueous solutions and d: nano-particles formed by CX8 and DNA molecule.
1
Rodik, R. V.; Boyko, V. I.; Kalchenko, V. I., Current Medicinal Chemistry 2009, 16, 1630.
2
Bagnacani, V.; Sansone, F.; Donofrio, G.; Baldini, L.; Casnati, A.; Ungaro, R., Organic Letters 2008,
10, 3953; Lalor, R.; DiGesso, J.L.; Mueller, A.; Matthews, S.E.: Chem. Commun., 2007, 4907.
3
Rodik, R.V., Jain, N., Miroshnichenko, S.I., Richert, L., Kalchenko, V.I., Mely, Y., Klymchenko, A. S.
Chemistry – A European Journal. In press.
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