Band 7, Heft 9

Drug design is an expensive and time-consuming process. Any method that allows reducing the time the costs of the drug development project can have great practical value for the pharmaceutical industry. In structure-based drug design, affinity prediction methods are of great importance. The majority of methods used to predict binding free energy in protein-ligand complexes use molecular mechanics methods. However, many limitations of these methods in describing interactions exist. An attempt to go beyond these limits is the application of quantum-mechanical description for all or only part of the analyzed system. However, the extensive use of quantum mechanical (QM) approaches in drug discovery is still a demanding challenge. This chapter briefly reviews selected methods used to calculate protein-ligand binding affinity applied in virtual screening (VS), rescoring of docked poses, and lead optimization stage, including QM methods based on molecular simulations.

Since 3000 B.C., evergreen plant Thea sinensis ( Theaceae ) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

Dynamic magnetic measurements on magnetic nanoparticle (MNP) samples have been widely used for the determination of structural MNP parameters as well as for the realization of bioassays. On the other hand, proposed that the MNPs are thermally blocked, i.e., that the dynamics are dominated by the Brownian rotation, and knowing the distribution of their hydrodynamic size, information on the matrix properties can be obtained. In contrast to conventional rheology, the local environment of the MNPs is sensed on the nanoscale so that important information on the embedding of MNPs in the matrix and thus the particle-matrix interaction is obtained. Depending on the characteristic length scales of the matrix and the size of the MNPs, rheological parameters, such as viscosity and shear modulus, derived from nanorheological measurements can differ from the values obtained from conventional rheology. To measure the MNP dynamics, different experimental techniques can be applied. In this contribution, the focus lies on ac susceptometry and fluxgate magnetorelaxometry. The analysis of the complex ACS spectra is generally carried out within a modified Debye model. Different approaches for the estimation of rheological parameters from the complex ACS spectra will be presented. Two model systems will exemplarily be discussed in detail. As a Newtonian matrix system, water-glycerol mixtures were studied. It is demonstrated that the dynamic viscosity can accurately be estimated from ACS measurements on well thermally blocked single-core as well as on multicore MNP systems, which include Brownian and Néel dynamics. As a viscoelastic matrix system, aqueous gelatin solutions were studied. Gelatin is known to be a Voigt-Kelvin model system, in which elastic and viscous forces are parallel. In particular, we studied the gelation dynamics by repetitive measurements of the complex ACS spectrum. Different approaches to derive viscosity and shear modulus are applied and compared. In order to identify magnetoviscous effects in dynamic magnetic measurements, the magnetic field dependence of the Brownian relaxation time has to be eliminated. ACS measurements on various sufficiently strongly diluted aqueous MNP suspensions were performed in dependence of ac field amplitude and superimposed dc field strength and compared to theory. Excellent agreement was found.

The integration of nanoparticles with magnetic, ferroelectric or semiconducting properties into liquid crystals (LCs) has attracted great interest both for fundamental investigations and for technological applications. Here, an overview of hybrid materials based on magnetic nanoparticles (MNPs) and thermotropic LCs is given. After a general introduction to thermotropic LCs and LC-MNP hybrid materials, various preparation methods established by us are presented. The synthesis of shape-(an)isotropic MNPs, their functionalization by tailored (pro)mesogenic ligands with linear or dendritic structures and their integration into LC hosts are discussed. The characterization of the MNPs, (pro)mesogenic ligands and resulting MNP-LC hybrid materials is described to show the influence of MNP functionalization on the MNP-LC interactions including aspects such as colloidal stability and structuring in the LC host. Overall, we show that the physical properties of the hybrid material are significantly influenced not only by the MNPs (i.e., their size, shape and composition) but also by their surface properties (i.e., the structure of the (pro)mesogenic ligands).

Interactions between magnetic nanoparticles and an anisotropic environment give rise to a variety of new magneto-optical, rheological and mechanical phenomena. This opens new avenues for developing novel multifunctional materials. In the course of this project, we investigated three types of anisotropic systems: dispersions of shape-anisotropic nanocrystals, magnetically doped molecular and colloidal liquid crystals, and organoferrogels. They were investigated by means of magneto-optical observations and by a magneto-mechanical torsion pendulum method.