Luminescent cyclometalated platinum compounds with N, P, and O^O ligands: Density-functional theory studies and analysis of the anticancer potential

Luminescent platinum cyclometalated complexes are species of interest mainly due to their applications in the optoelectronic and biological fields, especially with regard to their anticancer activity. Given this level of interest, a series of cyclometalated (2-[2′-thienyl]pyridinate, thpy and 2-[2,4-difluorophenyl]pyridinate, dfppy) platinum complexes with N-donor, PTA (1,3,5-triaza-7-phosphaadamantane) or chrysin-derived ligands (incorporating piperidine, HL1, or morpholine, HL2, fragments) were synthesized. The complexes are luminescent with tunable emission wavelengths. Aggregation in solution was observed for [Pt(dfppy)L1], 5. Density-functional theory (DFT) studies provided descriptions of the highest occupied molecular orbital (HOMO) and least unoccupied molecular orbital (LUMO) characteristics and their influence on the photophysical properties. The orbitals of 5–6 were different in nature to those of 1–4. Time-dependent DFT (TD-DFT) calculations showed that for 1–4 the excited states S1 and T1 reflect metal-to-ligand charge transfer (MLCT) and ligand-centered (LC) (C^N) contributions while for 5–6 these states are an LC transition centered on L1 or L2. The speciation in DMSO and DMSO/H2O was evaluated. Biological studies showed that [Pt(thpy)Cl(Hthpy)], 1, [Pt(dfppy)Cl(Hdfppy)], 2, and 5 exert significant cytotoxic activity against human cervical (HeLa) and lung (A549) carcinoma cells. The cytotoxicity of 1 increased 2.84-fold upon irradiation (blue). Microscopy assays on 5 showed that this compound accumulates in cytoplasmic organelles, preferentially in mitochondria. Mitochondrial metabolism was disrupted by the activity of the complexes, leading to a decline in the adenosine triphosphate (ATP) cellular content. Overall, the results show an alternative anticancer activity for complexes 1, 2, and 5, which could be of great interest for the treatment of tumors with acquired resistance to conventional DNA-targeted anticancer drugs.Los complejos ciclometalados de platino luminiscentes son especies de interés debido principalmente a sus aplicaciones en los campos optoelectrónico y biológico, especialmente en lo que se refiere a su actividad anticancerígena. Dado este nivel de interés, se sintetizaron una serie de complejos ciclometalados (2-[2′-tienil]piridinato, thpy y 2-[2,4-difluorofenil]piridinato, dfppy) de platino con N-donante, PTA (1,3,5-triaza-7-fosfaadamantano) o ligandos derivados de crisina (incorporando fragmentos de piperidina, HL1, o morfolina, HL2). Los complejos son luminiscentes con longitudes de onda de emisión sintonizables. Se observó agregación en solución para [Pt(dfppy)L1], 5. Los estudios de teoría del funcional de la densidad (DFT) proporcionaron descripciones de las características del orbital molecular de mayor ocupación (HOMO) y del orbital molecular de menor desocupación (LUMO) y su influencia en las propiedades fotofísicas. Los orbitales de 5-6 eran de naturaleza diferente a los de 1-4. Los cálculos DFT dependientes del tiempo (TD-DFT) mostraron que para 1-4 los estados excitados S1 y T1 reflejan la transferencia de carga metal-ligando (MLCT) y contribuciones centradas en el ligando (LC) (C^N) mientras que para 5-6 estos estados son una transición LC centrada en L1 o L2. Se evaluó la especiación en DMSO y DMSO/H2O. Los estudios biológicos mostraron que [Pt(thpy)Cl(Hthpy)], 1, [Pt(dfppy)Cl(Hdfppy)], 2 y 5 ejercen una actividad citotóxica significativa frente a células humanas de carcinoma cervical (HeLa) y pulmonar (A549). La citotoxicidad de 1 se multiplicó por 2,84 tras la irradiación (azul). Los ensayos de microscopía con 5 mostraron que este compuesto se acumula en orgánulos citoplasmáticos, preferentemente en mitocondrias. El metabolismo mitocondrial se vio alterado por la actividad de los complejos, lo que provocó una disminución del contenido celular de adenosín trifosfato (ATP). En conjunto, los resultados muestran una actividad anticancerígena alternativa para los complejos 1, 2 y 5, que podría ser de gran interés para el tratamiento de tumores con resistencia adquirida a los fármacos anticancerígenos convencionales dirigidos al ADN

Thermal stability and rheological properties of the 'non-stick' Caf1 biomaterial

WOS:000410928400001PubMed:28632140The ability to culture cells in three-dimensions has many applications, from drug discovery to wound healing. 3D cell culture methods often require appropriate scaffolds that mimic the cellular environments of different tissue types. The choice of material from which these scaffolds are made is of paramount importance, as its properties will define the manner in which cells interact with the scaffold. Caf1 is a protein polymer that is secreted from its host organism, Yersinia pestis, to enable escape from phagocytosis. In vitro, cells adhere poorly to the protein unless adhesion motifs are specifically introduced. Caf1 is a good candidate biomaterial due to its definable bioactivity, economical production and its ability to form hydrogels, through the use of cross-linkers. In this study, the thermostability of Caf1 was tested over a range of chemical conditions, and an initial characterisation of its rheological properties conducted in order to assess the suitability of Caf1 as a biomedical material. The results show that Caf1 retains its high thermostability even in harsh conditions such as extremes of pH, high salt concentrations and the presence of detergents. In solution, the concentrated polymer behaves as a complex viscous liquid. Due to these properties, Caf1 polymers are compatible with 3D bioprinting technologies and could be made to form a stimuliresponsive biomaterial that can alter its macrorheological properties in response to external factors. Caf1 biomaterials could therefore prove useful as 3D cell scaffolds for use in cell culture and wound repair.Industrial Biotechnology Catalyst (Innovate UK); Industrial Biotechnology Catalyst (BBSRC); Industrial Biotechnology Catalyst (EPSRC)Engineering & Physical Sciences Research Council (EPSRC); Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)This project has been funded by the Industrial Biotechnology Catalyst (Innovate UK, BBSRC, EPSRC) to support the translation, development and commercialisation of innovative Industrial Biotechnology processes. Y Ulusu was funded by the Scientific and Technological Research Council of Turkey (TUBITAK) on the International Post-Doctoral Research Fellowship Programme

Cell-free protein synthesis in hydrogel materials

We report a method for embedding cell-free protein synthesis reactions in macro-scale hydrogel materials without a free liquid phase. This paper focuses on methods of preparation for a variety of hydrogels and an investigation of the impact that the hydrogel material has on cell-free protein synthesis

Hierarchical self-assembly in an RNA-based coordination polymer hydrogel

An RNA-based coordination polymer is formed by the aqueous reaction of CuI ions with the thionucleoside enantiomer (−)6-thioguanosine, (6tGH). The resulting polymer, [CuI(μ3-S-thioG)]n1, has a one-dimensional structure based on a [Cu4–S4] core and undergoes extensive hierarchical self-assembly transforming from oligomeric chains → rod → cable → bundle through which a fibrous gel forms, that undergoes syneresis to form a self-supporting mass. The assembly involves the formation of helical cables/bundles and, in combination with the intrinsic photoemission of the polymer, results in the material exhibiting circularly polarised luminescence (CPL)

Circularly polarised luminescence in an RNA-based homochiral, self-repairing, coordination polymer hydrogel

The aqueous equimolar reaction of Ag(I) ions with the thionucleoside enantiomer (−)6-thioguanosine, ((−)6tGH), yields a one-dimensional coordination polymer {Ag(−)tG}n, the self-assembly of which generates left-handed helical chains. The resulting helicity induces an enhanced chiro-optical response compared to the parent ligand. DFT calculations indicate that this enhancement is due to delocalisation of the excited state along the helical chains, with 7 units being required to converge the calculated CD spectra. At concentrations ≥15 mmol l−1 reactions form a sample-spanning hydrogel which shows self-repair capabilities with instantaneous recovery in which the dynamic reversibility of the coordination chains appears to play a role. The resulting gel exhibits circularly polarised luminescence (CPL) with a large dissymmetry factor of −0.07 ± 0.01 at 735 nm, a phenomenon not previously observed for this class of coordination polymer