Organometallic Ru, Os, Rh and Ir half-sandwich conjugates of ispinesib - impact of the organometallic group on the antimitotic activity.

Antimitotic agents are among the most important drugs used in anticancer therapy. Kinesin spindle protein (KSP) was proposed as a promising target for new antimitotic drugs. Herein, we report the synthesis of Ru, Os, Rh, and Ir half-sandwich complexes with the KSP inhibitor ispinesib and its (S)-enantiomer. Conjugation of the organometallic moiety with ispinesib and its (S)-enantiomer resulted in a significantly increased cytotoxicity of up to 5.6-fold compared to the parent compounds, with IC50 values in the nanomolar range. The most active derivatives were the ispinesib Ru and Rh conjugates which were able to generate reactive oxygen species (ROS), which may at least partially explain their high cytotoxicity. At the same time, the Os and Ir derivatives acted as KSP inhibitors with no effects on ROS generation.

Difluoroborate-based bichromophores: Symmetry relaxation and two-photon absorption.

Given potential applications of multiphoton absorbers, in the present work we have studied the symmetry-relaxation effects in one- and two-photon absorption spectra in two bichromophore systems based on difluoroborate core linked by biphenylene or bianthracene moieties. We have employed a palette of experimental methods (synthesis, one- and two-photon spectroscopy, X-ray crystallography) and state-of-the-art computational methods to shed light on how symmetry relaxation, a result of twisting of building blocks, affects one- and two-photon absorption of the two studied fluorescent dyes. Electronic-structure calculations revealed that the planarity of central biphenyl moiety, as well as deviations from planarity up to 30-40 deg., ensure maximum values of two-photon transition strengths. Perpendicular arrangement of phenylene units in biphenylene moiety leads to 20% drop in the two-photon transition strengths. More detailed studies demonstrated that equilibrium structures of both compounds in chloroform solution show very different values of two-photon absorption cross sections at absorption band maxima, i.e. 224 GM for and 134 GM for biphenyle and bianthracene linkers, respectively. The latter value is in good agreement with experimental value obtained using Z-scan method. The difference in two-photon absorption cross section between both compounds can be rationalized based on equilibrium geometry differences, i.e. interplanar angle is 35 deg and 91 deg in the case of biphenylene and bianthracene moiety, respectively. It is thus not beneficial to introduce conformationally locked central linker based on bianthracene moiety.

Bioconjugation Strategy for Ceramic Membranes Decorated with Candida Antarctica Lipase B-Impact of Immobilization Process on Material Features.

A strategy for the bioconjugation of the enzyme Candida antarctica lipase B onto titania ceramic membranes with varied pore sizes (15, 50, 150, and 300 kDa) was successfully performed. The relationship between the membrane morphology, i.e.,the pore size of the ceramic support, and bioconjugation performance was considered. Owing to the dimension of the enzyme (~33 kDa), the morphology of the ceramics allowed (50, 150, and 300 kDa) or did not allow (15 kDa) the entrance of the enzyme molecules into the porous structure. Such a strategy made it possible to better understand the changes in the material (morphology) and physicochemical features (wettability, adhesiveness, and surface charge) of the samples, which were systematically examined. The silane functionalization and enzyme immobilization were accomplished via the covalent route. The samples were characterized after each stage of the modification, which was very informative from the material point of view. As a consequence of the modification, significant changes in the contact angle, roughness, adhesion, and zeta potential were observed. For instance, for the 50 kDa membrane, the contact angle increased from 29.1 ± 1.5° for the pristine sample to 72.3 ± 1.5° after silane attachment; subsequently, it was reduced to 57.2 ± 1.5° after the enzyme immobilization. Finally, the contact angle of the bioconjugated membrane used in the enzymatic process rose to 92.9 ± 1.5°. By roughness (Sq) controlling, the following amendments were noticed: for the pristine 50 kDa membrane, Sq = 1.87 ± 0.21 µm; after silanization, Sq = 2.33 ± 0.30 µm; after enzyme immobilization, Sq = 2.74 ± 0.26 µm; and eventually, after the enzymatic process, Sq = 2.37 ± 0.27 µm. The adhesion work of the 50 kDa samples was equal to 136.41 ± 2.20 mN m-1 (pristine membrane), 94.93 ± 2.00 mN m-1 (with silane), 112.24 ± 1.90 mN m-1 (with silane and enzyme), and finally, 69.12 ± 1.40 mN m-1 (after the enzymatic process). The materials and physicochemical features changed substantially, particularly after the application of the membrane in the enzymatic process. Moreover, the impact of ceramic material morphology on the zeta potential value is here presented for the first time. With an increase in the ceramic support cut-off, the amount of immobilized lipase rose, but the specific productivity was higher for membranes possessing smaller pores, owing to the higher grafting density. For the enzymatic process, two modes of accomplishment were selected, i.e., stirred-tank and cross-flow. The latter method was characterized by a much higher effectiveness, with a resulting productivity equal to 99.7 and 60.3 µmol h-1 for the 300 and 15 kD membranes, respectively.

Highly effective enzymes immobilization on ceramics: Requirements for supports and enzymes.

Enzyme immobilization is a well-known method for the improvement of enzyme reusability and stability. To achieve very high effectiveness of the enzyme immobilization, not only does the method of attachment need to be optimized, but the appropriate support must be chosen. The essential necessities addressed to the support applied for enzyme immobilization can be focused on the material features as well as on the stability and resistances in certain conditions. Ceramic membranes and nanoparticles are the most widespread supports for enzyme immobilization. Hence, the immobilization of enzymes on ceramic membrane and nanoparticles are summarized and discussed. The important properties of the supports are particle size, pore structure, active surface area, volume to surface ratio, type and number of reactive available groups, as well as thermal, mechanical, and chemical stability. The modifiers and the crosslinkers are crucial to the enzyme loading amount, the chemical and physical stability, and the reusability and catalytical activity of the immobilized enzymes. Therefore, the chemical and physical methods of modification of ceramic materials are presented. The most popular and used modifiers (e.g. APTES, CPTES, VTES) as well as activating agents (GA, gelatin, EDC and/or NHS) applied to the grafting process are discussed. Moreover, functional groups of enzymes are presented and discussed since they play important roles in the enzyme immobilization via covalent bonding. The enhanced physical, chemical, and catalytical properties of immobilized enzymes are discussed revealing the positive balance between the effectiveness of the immobilization process, preservation of high enzyme activity, its good stability, and relatively low cost.

Atypical Cardiac Location of Melanoma of Unknown Origin.

The subject was a 66-year-old woman, suffering from the chest pain evoked by physical activity. Transthoracic echocardiography (TTE) revealed an abnormal structure, 41 × 29 mm. In MSCT, a hypodensic mobile tissue lesion that was infiltrating the whole thickness of left ventricle was confirmed. PET excluded the existence of other remote lesions. After surgical tumor removal, histopathological differential diagnosis revealed melanoma, myoepithelial cancer, and MPNST "high-grade" sarcoma. A control TTE detected a tumor that was 14 × 10 mm. After immunohistochemical results, immunotherapy with pembrolizumab was used, which resulted in complete tumor resolution. Presently, surgical resection and neoadjuvant targeted immunochemotherapy remain the treatment of choice for clinical stage III/IV melanoma.

Molecular Decoration of Ceramic Supports for Highly Effective Enzyme Immobilization-Material Approach.

A highly effective method was developed to functionalize ceramic supports (Al2O3 powders and membranes) using newly synthesized spacer molecules. The functionalized materials were subsequently utilized for Candida antarctica lipase B enzyme immobilization. The objective is to systematically evaluate the impact of various spacer molecules grafted onto the alumina materials will affect both the immobilization of the enzymes and specific material surface properties, critical to enzymatic reactors performance. The enzyme loading was significantly improved for the supports modified with shorter spacer molecules, which possessed higher grafting effectiveness on the order of 90%. The specific enzyme activity was found to be much higher for samples functionalized with longer modifiers yielding excellent enantioselectivity >97%. However, the enantiomeric ratio of the immobilized lipase was slightly lower in the case of shorter spacer molecules.

The Impact of Crystal Packing and Aurophilic Interactions on the Luminescence Properties in Polymorphs and Solvate of Aroylacetylide-Gold(I) Complexes.

The influence of the chemical substitution, crystal packing, and aurophilic interactions of the gold(I) acetylide complexes of the type (ArCOC≡C)n AuPEt3 (n=1,2) on their luminescent properties were examined. All described complexes undergo ligand scrambling in solution, which results in the formation of stable, easily isolated crystals that contain [ArCO(C≡C)n ]2 Au- (Et3 P)2 Au+ homoleptic species. In particular, we observed that the (benzoylacetylide)gold(I) complex yields three crystal forms with strikingly different luminescence properties. We monitored the conversion pathway for these forms: an orange luminescent form of homoleptic complex upon drying undergoes spontaneous transformation to bright green fluorescent form and finally to the weakly blue emissive one. In addition, we report a rare example of a helical arrangement of Au⋅Au⋅Au chains that are observed for the first time in acetylide gold(I) complexes in the case of heteroleptic (benzoylacetylide)gold(I) complex. This is a very rare case in which crystal structures and ensuing electronic properties of the heteroleptic and AuI complexes could be directly compared.

Functionalization of the "Bay Region" of Perylene in Reaction with 1-Arylalk-2-yn-1-ones Catalyzed by Trifluoromethanesulfonic Acid: One-Step Approach to 1-Acyl-2-alkylbenzo[ ghi]perylenes.

We describe a convenient method of the synthesis of 1-acyl-2-alkylbenzo[ ghi]perylenes via functionalization of the "bay region" of perylene in the reaction with 1-arylalk-2-yn-1-ones catalyzed by trifluoromethanesulfonic acid. We showed that the formation of 1-acyl-2-alkylbenzo[ ghi]perylenes from perylene and 1-arylalk-2-yn-1-ones might occur via spontaneous aromatization of 1-acyl-2-alkyl-2a,12a-dihydrogenbenzo[ ghi]perylenes by oxidation with dioxygen or by the hydrogen transfer to 1-arylalk-2-yn-1-ones. These compounds are fluorescent in solution with a high Stokes shift and with a ΦF value of up to 0.17 (and 0.36 in solid).

(Ar-CO-C[triple bond, length as m-dash]C)(PEt3)Au and (Ar-C[triple bond, length as m-dash]C)(PEt3)Au complexes bearing pyrenyl and ferrocenyl groups: synthesis, structure, and luminescence properties.

Two types of (acetylide)(triethylphosphine)gold(i) complexes ArCOC[triple bond, length as m-dash]CAuPEt3 (1a and 1b) and ArC[triple bond, length as m-dash]CAuPEt3 (2a and 2b) bearing Ar = pyren-1-yl or ferrocenyl group were synthesized and the effect of a carbonyl moiety on the structure, propensity to ligand scrambling in solution and luminescence properties were investigated. We found that the complexes bearing acetylenic ketone-derived ligands underwent ligand scrambling in solution to afford mixtures of ArCOC[triple bond, length as m-dash]CAuPEt3 and [(ArCOC[triple bond, length as m-dash]C)2Au]-[Au(PEt3)2]+. The latter complexes were isolated and their structures were confirmed by single crystal X-ray diffraction studies. The aurophilic interaction of AuAu in these complexes resulted in the formation of wire-like structures.