Maxim P. Evstigneev

On the Origin of C60 Fullerene Solubility in Aqueous Solution

In this work, we report that the surface hydroxylation of C60 molecules is the most likely mechanism for pristine C60 fullerenes/C60 fullerene aggregate stabilization in water, being independent of the method of C60 fullerene aqueous solution preparation.

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. The results provide a physicochemical basis for a potentially new biotechnological application of fullerenes as modulators of biological activity of aromatic drugs.

1H NMR investigation of the hetero-association of aromatic molecules in aqueous solution: factors involved in the stabilization of complexes of daunomycin and acridine drugs

Hetero-association of the anthracycline drug, daunomycin (DAU), with typical mutagens, the acridine dyes proflavine (PF) and acridine orange (AO), has been studied by 500 MHz 1H NMR spectroscopy as a function of concentration and temperature in 0.1 mol dm−3 phosphate buffered aqueous solutions at pD = 7.1. The results have been analysed in terms of a statistical-thermodynamical model of hetero-association of aromatic molecules, described previously [Davies, D. B., Veselkov, D. A., and Veselkov, A. N., 1999, Molec. Phys., 97, 439], but generalized in this work, so that there is no limitation on the magnitudes of the self-association constants of the interacting molecules. Expressions suitable for the analysis of NMR parameters of both components in the mixed solution have been developed enabling both the structural and thermodynamic properties of hetero-association to be determined. The magnitude of the equilibrium constant for hetero-association of PF + DAU is found to be substantially higher than the self-association constants of these molecules, whereas that for hetero-association of AO + DAU is intermediate between the equilibrium constants of self-association of AO and DAU. Intermolecular cross-peaks observed in 2D-ROESY spectra of PF + DAU mixed solutions are consistent with formation of a hetero-association complex in which an intermolecular hydrogen bond can form between either of the 3,6-diamino groups of the PF chromophore and the 9-MeCO group of DAU, which is in contrast to AO + DAU hetero-association, where such hydrogen bonds are unable to form. Quantitative structural and thermodynamical analysis of PF + DAU complexation is consistent with an intermolecular hydrogen bond contributing to the stability of the hetero-complex in aqueous solution. The NMR results show that hydrophobic interactions play a substantial role in the stabilization of the AO-DAU complex, characterized by a relatively small entropy change on complexation, compared to the PF-DAU hetero-complex, which is mainly stabilized by hydrogen bond and dispersive van der Waals interactions.

Structural Features of Highly Stable Reproducible C60 Fullerene Aqueous Colloid Solution Probed by Various Techniques

The method of preparation of highly stable reproducible C60 fullerene aqueous colloid solution is described. The structural organization of C60 fullerenes in aqueous solution was studied and analyzed in detail using various techniques such as chemical analysis, UV/VIS spectroscopy, atomic force and scanning tunneling microscopy, dynamic light scattering, and zeta potential methods.

Partition of thermodynamic energies of drug–DNA complexation

We report a computation methodology, which leads to the ability to partition the Gibbs free energy for the complexation reaction of aromatic drug molecules with DNA. Using this approach, it is now possible to calculate the absolute values of the energy contributions of various physical factors to the DNA binding process, whose summation gives a value that is reasonably close to the experimentally measured Gibbs free energy of binding. Application of the methodology to binding of various aromatic drugs with DNA provides an answer to the question “What forces are the main contributors to the stabilization of aromatic ligand–DNA complexes?”

A general nuclear magnetic resonance analysis of hetero-association of aromatic molecules in aqueous solution

A general nuclear magnetic resonance analysis of a statistical-thermodynamical model of hetero-association of aromatic molecules in solution has been developed to take “edge effects” into consideration, i.e., the dependence of proton chemical shifts on the position of the molecule situated inside or at the edge of the aggregate. This generalized approach is compared with a previously published model, where an average contribution to proton shielding is considered irrespective of the position of the molecule in the stack. Association parameters have been determined from experimental concentration and temperature dependences of 500 MHz proton chemical shifts of the hetero-association of the acridine dye, proflavine, and the phenanthridinium dye, ethidium bromide, in aqueous solution. Differences in the parameters in the range 10%–30% calculated using the basic and generalized approaches have been found to depend substantially on the magnitude of the equilibrium hetero-association constant Khet—the larger th...

Electrostatic contribution to the energy of binding of aromatic ligands with DNA

The method of solution of the nonlinear Poisson-Boltzmann equation was used to calculate electrostatic energy of binding of various aromatic ligands with DNA oligomers of different length. Analysis of the electrostatic contribution was made in terms of a two-step DNA binding process: formation of the intercalation cavity and insertion of the ligand. The total electrostatic energy was also partitioned into components: the energy of atom-atom coulombic interactions and the energy of interaction with surrounding water. The results indicate that electrostatic interactions are, as a whole, unfavorable to the intercalation process and that a correct analysis of structure-energy interrelation for Ligand-DNA interactions should only be accomplished at the level of the components rather than at the level of total electrostatic energy.

Self-association of the antitumour agent novatrone (mitoxantrone) and its hetero-association with caffeine

The self-association of the antitumour drug, novatrone, NOV (mitoxantrone) and its hetero-association with caffeine (CAF) have been investigated by 1D and 2D 500 MHz 1H NMR spectroscopy. Two-dimensional homonuclear correlation NMR spectroscopy (2D TOCSY and 2D ROESY) has been used for complete assignment of proton signals and for a qualitative analysis of the mutual arrangements of the aromatic drug molecules in the aggregates. The structural and thermodynamical parameters of molecular self- and hetero-association of the aromatic compounds have been determined from measurements of the NMR chemical shifts of the drug protons as a function of concentration and temperature. The self-association of NOV has been analysed using both the indefinite cooperative and non-cooperative models, and the hetero-association of NOV and CAF has been analysed in terms of a statistical-thermodynamical model, in which molecules form indefinite aggregates for both self- and hetero-association. The magnitudes of parameters (equilibrium reaction constants, enthalpy (ΔH) and entropy (ΔS)) have been calculated for self-association of NOV and its complexation with CAF; at 318 K the equilibrium constant for self-association of NOV is 12400 (±4000) l mol−1 and for hetero-association with CAF is 256 (±30) l mol−1. The most favourable structures of the NOV dimer and the 1∶1 NOV–CAF hetero-association complexes have been determined from the calculated limiting values of the induced chemical shifts of the drug protons.

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.

Profiles of equilibrium constants for self-association of aromatic molecules

Analysis of the noncovalent, noncooperative self-association of identical aromatic molecules assumes that the equilibrium self-association constants are either independent of the number of molecules (the EK-model) or change progressively with increasing aggregation (the AK-model). The dependence of the self-association constant on the number of molecules in the aggregate (i.e., the profile of the equilibrium constant) was empirically derived in the AK-model but, in order to provide some physical understanding of the profile, it is proposed that the sources for attenuation of the equilibrium constant are the loss of translational and rotational degrees of freedom, the ordering of molecules in the aggregates and the electrostatic contribution (for charged units). Expressions are derived for the profiles of the equilibrium constants for both neutral and charged molecules. Although the EK-model has been widely used in the analysis of experimental data, it is shown in this work that the derived equilibrium constant, K(EK), depends on the concentration range used and hence, on the experimental method employed. The relationship has also been demonstrated between the equilibrium constant K(EK) and the real dimerization constant, K(D), which shows that the value of K(EK) is always lower than K(D).