Quantum-chemical
calculations and molecular dynamics simulation
were applied to a model self-organization process of Congo red (CR)
molecules in aqueous solution and the impact of doxorubicin (DOX)
molecules on such a process. It was demonstrated that both pure CR/CR
and mixed CR/DOX dimers were stable. Van der Waals interactions between
aromatic units were responsible for a stacked dimer formation. An
important source of stabilization in the CR/CR dimer was the polarization
energy. In the CR/DOX mixed dimer long range, electrostatic interactions
were the main driving force leading to complexation. An implicit solvent
model showed that the formation of the CR/CR dimer was favored over
the CR/DOX one. Molecular dynamics simulations demonstrated rapid
complexation. In the pure CR system, short sequences of ribbon-like
structures were formed. Such structures might be glued by hydrogen
bonds to form bigger complexes. It was shown that the aromatic part
of the DOX molecule enters CR ribbons with the sugar part covering
the CR ribbons. These findings demonstrated that CR may find applications
as a carrier in delivering DOX molecules; however, further more extensive
investigations are required.
The uptake and distribution of doxorubicin in the MCF7 line of breast-cancer cells were monitored by Raman measurements. It was demonstrated that bioavailability of doxorubicin can be significantly enhanced by applying Congo red. To understand the mechanism of doxorubicin delivery by Congo red supramolecular carriers, additional monolayer measurements and molecular dynamics simulations on model membranes were undertaken. Acting as molecular scissors, Congo red particles cut doxorubicin aggregates and incorporated them into small-sized Congo red clusters. The mixed doxorubicin/Congo red clusters were adsorbed to the hydrophilic part of the model membrane. Such behavior promoted transfer through the membrane.
In the search for new carriers capable of transporting toxic drugs to a target, particular attention has been devoted to supramolecular systems with a ribbon-like micellar structure of which Congo red is an example. A special promise of the possible use of such systems for directing drugs to a target emerges from their particular affinity to immune complexes and as an independent property, binding many organic compounds including drugs by intercalation. Serum albumin also appeared able to bind micellar particles of such systems. It may protect them against dilution in transport. The mathematical tool, which relies on analysis of the distribution of polarity and hydrophobicity in protein molecules (fuzzy oil drop model), has been used to find the location of binding area in albumin as well as anchorage site for Congo red in heated IgG light chain used as a model presenting immunoglobulin-like structures. Results confirm the suggested formerly binding site of Congo red in V domain of IgG light chain and indicated the cleft between pseudo-symmetric domains of albumin as the area of attachment for the dye.
In view of the possible medical applications of saponins, the molecular structure of a GOTCAB saponin from the roots of Gypsophila paniculata L. was determined by NMR. The biological activity of saponins may depend on the interaction with cell membranes. To obtain more insight in the mechanism of membrane-related saponin function, an experimental and theoretical study was conducted. Ternary lipid systems composed of sphingomyelin, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and cholesterol were used as models of mammalian cell membranes. The membrane–saponin interaction was studied experimentally by monitoring surface pressure in the monomolecular films formed at the air–aqueous subphase interface. The behavior of GOTCAB saponin in a water box and model monolayer systems was characterized by molecular dynamics simulations. The results obtained showed that, in the systems used, cholesterol had a decisive effect on the interaction between GOTCAB and phosphocholine or sphingomyelin as well as on its location within the lipid film.
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