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ISSN 1998-9539

Amphiphilic Macrocyclic Derivative of Pyrimidine: Self-Assembly, Solubilization and Interaction with DNA Decamer

Dinar R. Gabdrakhmanov,@ Darya A. Samarkina, Vyacheslav E. Semenov, Lilya F. Saifina, and Lucia Ya. Zakharova
A.E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, 420088 Kazan, Russian Federation
@Corresponding author E-mail:
DOI: 10.6060/mhc171144g
Macroheterocycles 2017 10(4-5) 567-573
Using the set of physico-chemical methods (tensiometry (ring detachment method), conductometry, dynamic and electrophoretic light scattering, fluorescence spectroscopy and spectrophotometry) aggregation behavior and functional activity (solubilizing activity, complexation with DNA decamer) of dicationic pyrimidinophane bearing allyl fragment have been investigated. Critical aggregation concentration (cac) values determined by tensiometry and conductometry techniques correspond to 1 mM and 3 mM. Mismatches in the data obtained using two different methods could be explained by difference in their sensitivity. Obtained cac value coincides with that of earlier studied pyrimidinophane bearing n-decyl hydrophobic residues. This is the evidence of insignificant effect of the size of macrocycle and the nature of hydrophobic radical in pyrimidinic moiety on aggregation behavior of pyrimidinophanes, which aggregation behavior is mainly driven by the presence of intra- and intermolecular spacers between macrocycles. Solubilizing activity of amphiphilic pyrimidinophane toward hydrophobic azodye Orange OT, which has a band in electronic absorption spectrum with the maximum at 495 nm, has been examined by spectrophotometry technique. The presence of two aggregate types beyond cac with various solubilization power has been established: the first one corresponds to initiation of aggregates formation, while the second one reflects their morphological rearrangement. Possible reason of similar phenomenon is intermolecular π-stacking interactions of pyrimidinic moieties leading to the growth of aggregates. Calculated values of solubilizing power and aggregation numbers (by Schott technique) indicate on the fact, that the growth of aggregates is accompanied by loosing of pyrimidinophane molecules packing. As a result, aggregates are unable to withhold former amount of Orange OT. Using dynamic light scattering technique the size of pyrimidinophane aggregates in aqueous solutions has been estimated. Hydrodynamic diameter of associates formed was approximately 100 nm in the whole concentration range studied. However, additional minor peaks with hydrodynamic diameter ca. 300 nm appeared in concentrated solutions of pyrimidinophane. Similar size of particles in the system corresponds, to the best of our knowledge, to formation of layered or stacking aggregates (open mode of association). Data obtained by electrophoretic light scattering showed gradual increase of zeta potential values from +40 tо +80 mV. Similar behavior is typical for cationic surfactants and reflects the growth of aggregates size. For the estimation of binding capability of pyrimidinophane with DNA decamer (oligonucleotide) investigation of the size of mixed complexes (lipoplexes), its charge characteristics and binding degree between components have been involved. Estimation of particles size in pyrimidinophane/oligonucleotide binary system at various amount of macrocycle exhibited the formation of lipoplexes with mean hydrodynamic diameter in the range from 50 nm to 200 nm. This is in accordance with biotechnological requirements for similar complexes (hydrodynamic diameter must be less or equal to 200 nm for prolonged circulation in bloodstream). Electrophoretic titration of oligonucleotide solution by pyrimidinophane makes it possible to demonstrate inability of macrocyclic compound to compensate the negative charge of oligonucleotide. Steric hindrances for the localization of onium center in the area of negatively charged oligonucleotide phosphate groups could be considered as a cause of this phenomenon. Fluorescence analysis of ethidium bromide exclusion assay indicates on relatively high fraction of oligonucleotide bound with pyrimidinophane (maximum 90 %). Probably, in the case of this pyrimidinophane unconventional mechanism of binding with oligonucleotide is realized (interaction between hydrophobic domains of oligonucleotide and pyrimidinophane with minor contribution of electrostatic interactions).


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