Experimental and theoretical insights into the structure and molecular dynamics of 2,3,3',4'-tetramethoxy-trans-stilbene - a chemopreventive agent.

The methoxy analogue of a trans-stilbene compound - 2,3,3',4'-tetramethoxy-trans-stilbene - was selected to characterize its crystallographic structure, intermolecular interactions and molecular dynamics. The sample was studied using single-crystal X-ray diffraction (XRD), infrared spectroscopy (FT-IR), liquid and solid-state 1H and 13C nuclear magnetic resonance (NMR) and quasielastic neutron scattering (QENS). The compound crystallized in the orthorhombic Pbca space group. The experimental methods were supported by theoretical calculations, density functional theory (plane-wave DFT) and molecular dynamics simulations (MD) methods. Combining several experimental and simulation techniques allowed the detailed analysis of molecular reorientations and provided a consistent picture of the molecular dynamics. The internal molecular mobility of the studied compound can be associated with the reorientational dynamics of four methyl groups. Interestingly, a large diversity of the energy barriers was observed - one methyl group reoriented across low activation barriers (∼3 kJ mol-1), while three methyl groups exhibited a high activation energy (10-14 kJ mol-1) and they are characterised by very different correlation times differing by almost two orders of magnitude at room temperature. The intramolecular interactions mainly influence the activation barriers.

New Metallophthalocyanines Bearing 2-Methylimidazole Moieties-Potential Photosensitizers against Staphylococcus aureus.

Newly developed tetra- and octasubstituted methimazole-phthalocyanine conjugates as potential photosensitizers have been obtained. Synthesized intermediates and final products were characterized by the MALD-TOF technique and various NMR techniques, including 2D methods. Single-crystal X-ray diffraction was used to determine the crystal structures of dinitriles. The studied phthalocyanines revealed two typical absorption bands-the Soret band and the Q band. The most intense fluorescence was observed for octasubstituted magnesium(II) phthalocyanine in DMF (ΦFL = 0.022). The best singlet oxygen generators were octasubstituted magnesium(II) and zinc(II) phthalocyanines (Φ∆ 0.56 and 0.81, respectively). The studied compounds presented quantum yields of photodegradation at the level between 10-5 and 10-6. Due to their low solubility in a water environment, the liposomal formulations were prepared. Within the studied group, octasubstituted zinc(II) phthalocyanine at the concentration of 100 µM activated with red light showed the highest antibacterial activity against S. aureus equal to a 5.68 log reduction of bacterial growth.

Synthesis, biological evaluation and docking studies of trans-stilbene methylthio derivatives as cytochromes P450 family 1 inhibitors.

Cytochromes P450 family 1 (CYP1) are responsible for the metabolism of procarcinogens, for example polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines. The inhibition of CYP1 activity is examined in terms of chemoprevention and cancer chemotherapy. We designed and synthesized a series of trans-stilbene derivatives possessing a combination of methoxy and methylthio functional groups attached in different positions to the trans-stilbene skeleton. We determined the effects of synthesized compounds on the activities of human recombinant CYP1A1, CYP1A2 and CYP1B1 and, to explain the variation of inhibitory potency of methoxystilbene derivatives and their methylthio analogues, we employed computational analysis. The compounds were docked to CYP1A1, CYP1A2 and CYP1B1 binding sites with the use of Accelrys Discovery Studio 4.0 by the CDOCKER procedure. For CYP1A2 and CYP1B1, values of scoring functions correlated well with inhibitory potency of stilbene derivatives. All compounds were relatively poor inhibitors of CYP1A2 that possess the most narrow and flat enzyme cavity among CYP1s. For the most active CYP1A1 inhibitor, 2-methoxy-4'-methylthio-trans-stilbene, a high number of molecular interactions was observed, although the interaction energies were not distinctive.

(E)-1-[4-(Methyl-sulfan-yl)phen-yl]-2-(2,3,4-trimeth-oxy-phen-yl)ethene.

In the title compound, C(18)H(20)O(3)S, the rings are almost coplanar [inter-ring dihedral angle = 6.6 (2)°]. In the crystal, weak C-H⋯O hydrogen bonds between the meth-oxy groups connect adjacent mol-ecules, giving chains which extend along [001].

2-(4-Methyl-phen-yl)-2-oxoethyl 3-bromo-benzoate.

The mol-ecule of the title compound, C16H13BrO3, is built of two approximately planar fragments, viz. 3-bromo-benzoate [maximum deviation = 0.055 (2) Šand 2-oxo-2-p-tolyl-ethyl [maximum deviation = 0.042 (2) Å], inclined by 46.51 (7)°. In the crystal, weak C-H⋯O hydrogen bonds and Br⋯Br contacts [3.6491 (7) Å] connect the mol-ecules into infinite layers parallel to (-221).

1-(3-Chloro-phen-yl)-2-methyl-4-nitro-1H-imidazole-5-carboxamide.

In the crystal structure of the title compound, C(11)H(9)ClN(4)O(3), pairs of N-H⋯N(imidazole) hydrogen bonds connect the mol-ecules into centrosymmetric dimers, which are further connected by N-H⋯O(carbamo-yl) hydrogen bonds into C(4) chains along [010]. Inter-play of these two kinds of hydrogen bonds connect the mol-ecules into layers perpendicular to [101]. The imidazole [maximum deviation 0.0069 (9) Å] and phenyl rings are inclined at a dihedral angle of 58.44 (6)°; the nitro group is almost coplanar [dihedral angle 5.8 (2)°] with the imidazole ring while the carbamoyl group is almost perpendicular [70.15 (13)°] to it.

5-Chloro-1-phenyl-1H-pyrazol-4-amine.

In the crystal structure of the title compound, C(9)H(8)ClN(3), amino-pyrazole N-H⋯N hydrogen bonds connect the mol-ecules along the [010] direction; the chains interact with each other only by van der Waals-type inter-actions. The pyrazole and phenyl rings are inclined at a dihedral angle of 45.65 (6)°