ABSTRACT
The specific features of structural self-organization of C60 fullerene and antitumor drug cisplatin (Cis) in physiological solution (0.9% NaCl) have been investigated by means of small-angle neutron scattering, scanning electron and atomic force microscopies, as well as isothermal titration calorimetry, dynamic light scattering and UV-Vis spectroscopy. The formation of C60 + Cis complexes, has been reported, unveiling the mechanism of medico-biological synergy observed during administration of the mixture of these drugs.
Subject(s)
Antineoplastic Agents/chemistry , Cisplatin/chemistry , Fullerenes/chemistry , Calorimetry , Light , Microscopy, Atomic Force , Models, Molecular , Neutron Diffraction , Scattering, Radiation , Scattering, Small Angle , Sodium Chloride/chemistry , SolutionsABSTRACT
The aim of this paper was to provide the physico-chemical characterization of a key process leading to amplification of the antitumor effect of antibiotic Doxorubicin (Dox) in vivo and in vitro and occurring at the molecular level through complexation with C60 fullerene. A wide range of physico-chemical tools was used such as UV/Vis and NMR spectroscopies, atomic force microscopy, isothermal titration calorimetry and zeta-potential methods. The unusual thermodynamic behavior of the complexation process was reported, featuring unexpected and, to a certain extent, contradictory experimental observations. The explanation of the obtained results was proposed resulting in creation of a general view on aromatic drug binding with C60 fullerene. Based on these results some important practical outcomes for anticancer therapy were formulated.
Subject(s)
Anti-Bacterial Agents/chemistry , Doxorubicin/chemistry , Fullerenes/chemistry , Molecular StructureABSTRACT
A statistical-thermodynamical model of mixed association in which one component's self-association is unlimited while the second component does not self-aggregate is described. The model was tested with 4',6-diamidino-2-phenyl-indole-dihydrochloride (DAPI) and ethidium bromide (EB) using light absorption spectroscopy and calorimetry. The system is controlled by two parameters, which represent self-aggregation 'neighborhood' association constant KCC and mixed 'neighborhood' association constant KAC. Calculated, using this model, KAC = 58.2 +/- 1 M-1, KAC = 64.6 +/- 2 M-1 for DAPI and EB, respectively, are in good agreement with known values of stacking interactions. The titration microcalorimetric measurement of DAPI-CAF interaction delta H = -11.1 +/- 0.4 kcal/mol is also consistent with this type of reaction. The structures of the stacking complexes were also confirmed by semi-empirical molecular modeling in the presence of water. The data indicate that CAF forms stacking complexes with DAPI and EB, thus effectively lowering the concentration of the free ligands in the solution, and therefore, CAF can be used to modulate aromatic compound activity.
Subject(s)
Caffeine/chemistry , Ethidium/chemistry , Indoles/chemistry , Intercalating Agents/chemistry , Models, Chemical , Kinetics , Ligands , Models, Molecular , Solutions , Spectrophotometry , Thermodynamics , WaterABSTRACT
PpeI is a type II restriction endonuclease isolated from cyanobacterial strain Phormidium persicinum. The endonuclease PpeI, an isoschizomer of ApaI, recognizes the hexanucleotide sequence (5'-GGGCC/C-3') and cleaves, after the second C, producing four nucleotide 3'-cohesive ends.
