Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis, Characterisation and Application in Rhodium-Catalysed Hydroformylation.

Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (-)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)2(acac), was attested by 31P NMR, which presented a doublet in the range of δ = 120 ppm, with a 1J(103Rh-31P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm-1 and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.

Selecting the spin crossover profile with controlled crystallization of mononuclear Fe(iii) polymorphs.

Two polymorphic species of the [Fe(5-Br-salEen)2]ClO4 compound were obtained, each of them being selectively recovered after evaporation of the solvent at a controlled rate. While polymorph 1a is formed during slow evaporation, fast evaporation favors polymorph 1b. The importance of the evaporation rate was recognized after detailed studies of the reaction temperature, solvent evaporation rate and crystallization temperature effects. The complex in the new polymorphic form 1a showed an abrupt spin crossover at 172 K with a small 1 K hysteresis window and over a narrow 10 K range. 57Fe Mössbauer spectroscopy and differential scanning calorimetry, complemented by X-ray studies for both the high-spin and low-spin forms, were used to further characterize the new polymorphic phase 1a. Both polymorphs are based on the same Fe(iii) complex cation hydrogen bonded to the perchlorate anion. These units are loosely bound in the crystals via weak interactions. In the new polymorph 1a, the hydrogen bonds are stronger, while the weak hydrogen and halogen bonds, as well as π-π stacking, create a cooperative network, not present in 1b, responsible for the spin transition profile.

Dynamic spin interchange in a tridentate Fe(iii) Schiff-base compound.

The thermosalient effect is still a rare and poorly understood phenomenon, where crystals suddenly jump, bend, twist or explode upon undergoing a thermally activated phase transition. The synthesis and characterisation of the new spin transition Fe(iii) compound [Fe(5-Br-salEen)2][ClO4] (salEen = N-ethyl-N-(2-aminoethyl)salicylaldiminate) is described and its thermosalient behaviour reported. It is the first example of a thermosalient effect with a spin transition and magnetic, calorimetric, diffraction, microscopy and computational studies are used to characterise these effects. Both thermosalient effect and spin transition occur around 320 K upon heating and are accompanied by an anisotropic unit cell change with conservation of crystal symmetry that causes a large enough stress of the crystal lattice to induce crystal explosion. This stress can ultimately be traced back to a diffusionless and distortive structural perturbation resulting in a coupled spin transition-thermosalient effect.

Estudo de fase II do uso de paclitaxel e gencitabina como tratamento de resgate no câncer de mama metatástico / Phase II study of paclitaxel and gemcitabine in patients with metastatic breast cancer

O tratamento de resgate em portadoras de câncer de mama metastático (CMM) que falharam com esquemas à base de antracíclicos ainda apresenta resultados desapontadores. Por outro lado, a eficácia individual, o possível sinergismo e a quase ausência de toxicidade sobreposta entre o paclitaxel e a gencitabina tornaram essa associaçäo promosora no tratamento dessas pacientes. Nesse estudo prospectivo, pacientes portadoras de CMM já tratadas com, no mínimo, um esquema quimioterápico à base de antracíclicos foram alocadas para receber: paclitaxel - 175mg/m² no dia 1, em infusäo de três horas e gencitabina, 1,0g/m² nos dias 1 e 8 (G-1,8_, em ciclos repetidos a cada 21 dias, ambulatorialmente, por, no máximo, 8 ciclos. Vinte e nove pacientes foram alocadas para o estudo e avaliáveis. Tratamento prévio: fluouracil, adriamicina e ciclofosfamida - FAC (18 casos); fluouracil, epidorrubicina e coclofosfamida - FEC (4 casos), mitoxantrona/CMF (4 casos) e cisplatina, vimblastina e mitomicina C após falha ao FAC em 3 casos. Idade mediana: 46 anos (32-68). Foram administrados 137 ciclos (mediana de 4 por paciente). O regime foi bem tolerado e nenhum óbito decorreu do tratamento. Houve 16 (55 por cento) respostas objetivas (intervalo de confiança 95 por cento: 36 por cento-73 por cento), incluindo 5 (17 por cento) respostas completas e 11 (38 por cento) respostas parciais (intervalo de confiança 95 por cento: 3 por cento-30 por cento e 19 por cento-56 por cento, respectivamente). Seis (20,5 por cento) pacientes obtiveram estabilizaçäo da doença. Duraçäo mediana de respostas: 8 meses (variaçäo de 4 a 26); sobrevida mediana global: 12 meses (variaçäo de 4 a 28). As taxas de sobrevida de um e dois anos foram, respectivamente, de 45 por cento e 30 por cento. Esses resultados sugerem que tal a associaçäo estudada seja efetiva como tratamento de resgate no CMM, com toxicidade baixa e boa tolerabilidade, quando administrada no esquema G-1,8. Tais resultados necessitam agora ser confirmados em um estudo de fase III