C Fullerene Clusters Stabilize the Biologically Inactive Form of Topotecan.

There is a range of experimental proofs that biologically relevant compounds change their activity in the presence of C fullerene clusters in aqueous solution, which most frequently act as a nanoplatform for drug delivery. Inspired by this evidence, we made an effort to investigate the interaction of fullerene clusters with the antibiotic topotecan (TPT). This study proceeded in three steps, namely, UV/vis titration to confirm complexation and in vitro assays on proliferating and nonproliferating cells to elucidate the role of C fullerene in the putative change in TPT activity.

Interceptor potential of C fullerene aqueous solution: a comparative analysis using the example of the antitumor antibiotic mitoxantrone.

We performed a qualitative and quantitative analysis of intermolecular interactions in aqueous solution between the antitumor antibiotic mitoxantrone and C fullerene in comparison with interactions between the antibiotic and well-known aromatic molecules such as caffeine and flavin mononucleotide, commonly referred to as interceptor molecules. For these purposes, we obtained equilibrium hetero-association constants of these interactions using a UV/Vis titration experiment. Special attention was paid to the interaction of C fullerene with mitoxantrone, which has been quantified for the first time.

Interaction of pseudoephedrine and azithromycin with losartan: Spectroscopic, dissolution and permeation studies.

This study aims at investigating the potential effect of selected cationic drugs (azithromycin (AZN) and pseudoephedrine sulfate (PSD) on the dissolution profile and intestinal permeation of losartan potassium (LOS) that might occur due to ion pair salt formation. DSC, FT-IR and H NMR indicated the formation of ion pair salts between LOS and each of AZN and PSD. Based on NMR chemical shifts calculations, utilizing specialized software, the most likely structures of the salt were proposed and revealed interesting structural features.

The theory of interceptor-protector action of DNA binding drugs.

The review discusses the theory of interceptor-protector action (the IPA theory) as the new self-consistent biophysical theory establishing a quantitative interrelation between parameters measured in independent physico-chemical experiment and in vitro biological experiment for the class of DNA binding drugs. The elements of the theory provide complete algorithm of analysis, which may potentially be applied to any system of DNA targeting aromatic drugs. Such analytical schemes, apart from extension of current scientific knowledge, are important in the context of rational drug design for managing drug's response by changing the physico-chemical parameters of molecular complexation.

Hetero-association models of non-covalent molecular complexation.

The present review discusses the current state-of-the-art in building models enabling the description of non-covalent equilibrium complexation of different types of molecules in solution, which results in the formation of supramolecular structures different in length and composition (hetero-association or supramolecular multicomponent co-polymerisation). The description is focused on standard physical and chemical quantities such as experimental observables and equilibrium parameters of interaction (equilibrium constants and concentrations). The major partial cases of the hetero-association models, such as finite and indefinite isodesmic and cooperative complexations, and Benesi-Hildebrand and Langmuir adsorption models are considered.

Study of the properties of doxorubicin-resistant cells affected by acute leucosis.

The stiffness of cell membrane was found to be one of the factors determining resistance of a cell in vitro to antibiotic doxorubicin action. Membranes of surviving cells are negatively charged (-35 - -30 mV) and have high values of stiffness (2.2-5.

Determination of the equilibrium constant of C fullerene binding with drug molecules.

We report a new analytical method that allows the determination of the magnitude of the equilibrium constant of complexation, K, of small molecules to C fullerene in aqueous solution. The developed method is based on the up-scaled model of C fullerene-ligand complexation and contains the full set of equations needed to fit titration datasets arising from different experimental methods (UV-Vis spectroscopy, H NMR spectroscopy, diffusion ordered NMR spectroscopy, DLS). The up-scaled model takes into consideration the specificity of C fullerene aggregation in aqueous solution and allows the highly dispersed nature of C fullerene cluster distribution to be accounted for.

Effect of Nicotinamide on the Photolysis of Riboflavin in Aqueous Solution.

The photolysis of riboflavin (RF) in aqueous solution in the presence of nicotinamide (NA) by visible light has been studied in the pH range 1.0-12.0 and the various photoproducts have been identified as known compounds.

Hidden entropic contribution in the thermodynamics of molecular complexation.

It has become an axiom that the thermodynamic analysis of non-covalent molecular complexation is intrinsically model-dependent, i.e. the set of implicitly or explicitly introduced assumptions may strongly affect the thermodynamic parameters.

Complex of C60 Fullerene with Doxorubicin as a Promising Agent in Antitumor Therapy.

The main aim of this work was to evaluate the effect of doxorubicin in complex with C60 fullerene (C60 + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C60 + Dox complex action. We found that volume of tumor from mice treated with the C60 + Dox complex was 1.4 times less than that in control untreated animals.

C60 fullerene affects elastic properties and osmoregulation reactions of human lymphocytes.

The influence of aqueous solution of pristine C60 fullerene (C60FAS) on functional activity of lymphocytes from a healthy person was studied for the first time. By means of atomic force microscopy, it was found that C60FAS in a concentration of 0.1 mg/ml increases the stiffness of the lymphocyte membrane by 41% (p < 0.

Shape-independent model (SHIM) approach for studying aggregation by NMR diffusometry.

NMR diffusometry has been gaining wide popularity in various areas of applied chemistry for investigating diffusion and complexation processes in solid and aqueous phases. To date, the application of this method to study aggregation phenomena proceeding beyond the dimer stage of assembly has been restricted by the need for a priori knowledge of the aggregates' shape, commonly difficult to know in practice. We describe here a comprehensive analysis of aggregation parameter-dependency on the type and shape selected for modeling assembly processes, and report for the first time a shape-independent model (designated the SHIM approach), which may be used as an alternative in cases when information on aggregates' shapes is unavailable.

Theoretical description of metabolism using queueing theory.

A theoretical description of the process of metabolism has been developed on the basis of the Pachinko model (see Nicholson and Wilson in Nat Rev Drug Discov 2:668-676, 2003) and the queueing theory. The suggested approach relies on the probabilistic nature of the metabolic events and the Poisson distribution of the incoming flow of substrate molecules. The main focus of the work is an output flow of metabolites or the effectiveness of metabolism process.

Binding polynomial in molecular self-assembly.

In the present work the concept of a binding polynomial is revisited for the most widely used case of self-assembly of identical molecular units and results in the re-construction of a link to the grand partition function of such a system. It is found that if the self-assembly process is not pronounced (i.e.

Quantitative correlation of the in vitro biological effect with parameters of molecular complexation in mutagen-interceptor systems.

According to the theory of interceptor-protector action a quantitative link between the physico-chemical parameters of molecular complexation and in vitro biological effect in aromatic drug-interceptor systems must exist. In the present communication such link between relative change in mutagenicity of IQ-type aromatic mutagens on addition of aromatic interceptor molecules with equilibrium hetero-association constants of mutagen-interceptor complexation has been found using the published in vitro data in bacteria cell systems.

Interceptor effect of C60 fullerene on the in vitro action of aromatic drug molecules.

C60 fullerenes are spherical molecules composed purely of carbon atoms. They inspire a particularly strong scientific interest because of their specific physico-chemical properties and potential medical and nanotechnological applications. In this work we are focusing on studying the influence of the pristine C60 fullerene on biological activity of some aromatic drug molecules in human buccal epithelial cells.

Evidence of entropically driven C60 fullerene aggregation in aqueous solution.

In the present work, we report the first experimental evidence of entropically driven C60 fullerene aggregation in aqueous solution, occurring with nearly zero enthalpy change.

Spectroscopic study of proflavine adsorption on the carbon nanotube surface.

Despite the fact that non-covalent interactions between various aromatic compounds and carbon nanotubes are being extensively investigated now, there is still a lack of understanding about the nature of such interactions. The present paper sheds light on one of the possible mechanisms of interaction between the typical aromatic dye proflavine and the carbon nanotube surface, namely, π-stacking between aromatic rings of these compounds. To investigate such a complexation, a qualitative analysis was performed by means of ultraviolet visible, infrared, and nuclear magnetic resonance spectroscopy.

Thiazotropsin aggregation and its relationship to molecular recognition in the DNA minor groove.

Aggregated states have been alluded to for many DNA minor groove binders but details of the molecule-on-molecule relationship have either been under-reported or ignored. Here we report our findings from ITC and NMR measurements carried out with AIK-18/51, a compound representative of the thiazotropsin class of DNA minor groove binders. The free aqueous form of AIK-18/51 is compared with that found in its complex with cognate DNA duplex d(CGACTAGTCG)2.

C60 fullerene aggregation in aqueous solution.

In the present work we develop a novel approach for quantification of the energetics of C60 fullerene aggregation in aqueous media in terms of equilibrium aggregation constant KF. In particular, it is shown that the experimental determination of the magnitude of KF is possible only within the framework of the 'up-scaled aggregation model', considering the C60 fullerene water solution as a solution of fullerene clusters. Using dynamic light scattering (DLS) data we report the value, K(F) = 56,000 M(-1), which is in good agreement with existing theoretical estimates and the results of energetic analyses.

On the reliability of quantitation of biological effect in drug-interceptor-DNA systems.

Relative insensitivity of theoretical estimation of biological effect in drug-interceptor-DNA systems is found with respect to variation of parameters of quasiphysiological conditions. The "inertness" of the biological response, in part, justifies the use of parameters of intermolecular interaction, derived from independent physicochemical experiments, in estimation of relative biological effect in the theory of interceptor/protector action.

Complexation of C60 fullerene with aromatic drugs.

The contributions of various physical factors to the energetics of complexation of aromatic drug molecules with C(60) fullerene are investigated in terms of the calculated magnitudes of equilibrium complexation constants and the components of the net Gibbs free energy. Models of complexation are developed taking into account the polydisperse nature of fullerene solutions in terms of the continuous or discrete (fractal) aggregation of C(60) molecules. Analysis of the energetics has shown that stabilization of the ligand-fullerene complexes in aqueous solution is mainly determined by intermolecular van der Waals interactions and, to lesser extent, by hydrophobic interactions.

Development of an analytical approach to study a three-component hetero-association by means of spectrophotometry.

A case of 1:m:n complexation in a three-component system containing any possible heterocomplexes formed between the non-self-aggregating, absorbing ligand A and two self-aggregating, non-absorbing ligands B and C was considered for the first time in an application for molecular spectroscopy. All expressions necessary for full quantitative analysis of experimental data in three-component mixtures were obtained, viz., the law of conservation of mass and the expression for an experimentally observed parameter.

Relation between the change in DNA elasticity on ligand binding and the binding energetics.

The widespread use of tweezers for measurement of ligand-DNA binding parameters is based on the McGhee-von Hippel treatment of the DNA contour and persistence length as a function of concentration. The McGhee-von Hippel approach contains the basic assumption that the binding constant K is independent of the number of already bound ligands. However, the change in elasticity of DNA on binding affects the entropic part of the Gibbs free energy and, hence, the K value in a concentration-dependent manner, making the whole approach inconsistent.

Random versus sequential pathway of molecular self-assembly.

Two important assumptions are often made in the analysis of molecular self-assembly at equilibrium, viz., that sequential is preferred to random aggregation and that the equilibrium constants at each stage of aggregation are equal, though both assumptions have not been justified strictly. In the present work we show that molecular self-assembly leading to formation of linear polymers and proceeding in a random manner appears to be less entropically favored than sequential aggregation, which provides a physical background for assuming sequential aggregation when studying molecular self-assembly in solution.