Effect of substitution on the ultrafast deactivation of the excited state of benzo[b]thiophene-arylamines.

A complete and systematic study of the spectroscopic and photophysical properties of five novel diarylamines in the benzo[b]thiophene series (oligoanilines) was performed in solution at room (293 K) and low (77 K) temperature. The title compounds resulting from the link between one aniline unit with a benzo[b]thiophene unit (with two different methyl and methoxy substitution) were characterized using steady-state absorption, fluorescence and phosphorescence spectroscopy, as well as femto- to nano-second time resolved spectroscopies. The study involved the determination of the absorption, emission and triplet-triplet absorption together with all relevant quantum yields (fluorescence, phosphorescence, intersystem crossing, internal conversion and singlet oxygen yields), excited state lifetimes and the overall set of deactivation rate constants (kF, kIC and kISC). This study was further complemented with theoretical calculations, namely with the determination of the optimized ground-state molecular geometries for the diarylamines together with the prediction of the lowest vertical one-electron excitation energy and the relevant molecular orbital contours using DFT calculations. The DFT results were found to corroborate the observed charge-transfer character of the singlet excited state. The experimental results showed that the radiationless decay processes (internal conversion and intersystem-crossing) constitute the main excited state deactivation pathways and that substitution with methyl and methoxy groups induces significant changes in the spectroscopic and photophysical behaviour of these compounds. This was also corroborated by the femtosecond transient absorption study, where it was found that the ultrafast dynamics of the diarylamines was best described by a sequential model featuring fast solvent relaxation followed by conformational relaxation to a more planar excited state, from where singlet excited state deactivation occurs through internal conversion and competitive intersystem crossing (the latter giving rise to the formation of long lived triplet states). The high singlet oxygen quantum yield values obtained suggest that the triplet state is involved in the photodegradation processes of these compounds.

A new antitumoral Heteroarylaminothieno[3,2-b]pyridine derivative: its incorporation into liposomes and interaction with proteins monitored by fluorescence.

The fluorescence properties of the new potent antitumoral methyl 3-amino-6-(benzo[d]thiazol-2-ylamino)thieno[3,2-b]pyridine-2-carboxylate in solution and when encapsulated in several different nanoliposome formulations were investigated. The compound exhibits very reasonable fluorescence quantum yields and a solvent sensitive emission in several polar and non-polar media, despite not being fluorescent in protic solvents. Fluorescence anisotropy measurements of the compound incorporated into liposomes revealed that this thienopyridine derivative can be carried in the hydrophobic region of the lipid membrane. Liposome formulations including this antitumor compound are nanometric in size, with a diameter lower than 130 nm and generally low polydispersity, and are promising for future drug delivery developments. The interaction of the compound with bovine serum albumin (BSA) and the multidrug resistance protein MDR1 was monitored by FRET, the compound acting as an energy acceptor. It was observed that the drug had a lower interaction with the MDR1 protein than with the native form of BSA, which is an important result regarding applications of this antitumoral drug.

ChemT, an open-source software for building template-based chemical libraries.

In computational chemistry, vast quantities of compounds are generated, and there is a need for cheminformatic tools to efficiently build chemical compound libraries. Several software tools for drawing and editing compound structures are available, but they lack options for automatic generation of chemical libraries. We have implemented ChemT, an easy-to-use open-source software tool that automates the process of preparing custom-made template-based chemical libraries. ChemT automatically generates three-dimensional chemical libraries by inputting a chemical template and the functional groups of interest. The graphical user interface of ChemT is self-explanatory, and a complete tutorial is provided. Several file formats are accepted by ChemT, and it is possible to filter the generated compounds according to different physicochemical properties. The compounds can be subject to force field minimization, and the resulting three-dimensional structures recorded on commonly used file formats. ChemT may be a valuable tool for investigators interested in using in silico virtual screening tools, such as quantitative structure-activity relationship modelling or molecular docking, in order to prioritize compounds for further chemical synthesis. To demonstrate the usefulness of ChemT, we describe an example based on a thieno[3,2-b]pyridine template. ChemT is available free of charge from our website at http://www.esa.ipb.pt/~ruiabreu/chemt .

Synthesis of bis-amino acid derivatives by Suzuki cross-coupling, Michael addition and substitution reactions.

Several bis-amino acids were prepared using a bis-Suzuki coupling (compounds 4-8, 10), a sequential Michael addition and bis-Suzuki coupling (compounds 12, 13) and a Michael addition followed by a substitution reaction (compounds 18, 19). Thus, the pure stereoisomer of the methyl esters of N-(tert-butoxycarbonyl)-beta-bromodehydroaminobutyric acid and dehydrophenylalanine and of N-benzyloxycarbonyl-beta-bromodehydroaminobutyric acid were reacted with 1,4-phenylene-bis-boronic acid or 9,9-dioctyl-9H-fluorene-2,7-bis-boronic acid using modified Suzuki coupling conditions. The corresponding bis-dehydroamino acid derivatives were obtained in good to high yields maintaining the stereochemistry of the starting materials. This reaction was also applied successfully to a brominated dehydrodipeptide and 1,4-phenylene-bis-boronic acid showing that it could be used to create cross-links in peptide chains. An N,N-diacyldehydroalanine derivative was used in a sequential Michael addition and bis-Suzuki coupling giving a p-terphenyl bis-amino acid and a fluorenyl bis-amino acid in good yields. Two bis-alpha,beta-diamino acids were obtained by a Michael addition of 1,2,4-triazole to the methyl esters of N-(4-toluenesulfonyl), N-(tert-butoxycarbonyl) dehydroamino acids followed by treatment with ethylenediamine.

Photochemistry and photophysics of thienocarbazoles.

Two methylated thienocarbazoles and two of their synthetic nitro-precursors have been examined by absorption, luminescence, laser flash photolysis and photoacoustic techniques. Their spectroscopic and photophysical characterization involves fluorescence spectra, fluorescence quantum yields and lifetimes, and phosphorescence spectra and phosphorescence lifetimes for all the compounds. Triplet-singlet difference absorption spectra, triplet molar absorption coefficients, triplet lifetimes, intersystem crossing S1 --> T1 and singlet molecular oxygen yields were obtained for the thienocarbazoles. In the case of the thienocarbazoles it was found that the lowest-lying singlet and triplet excited states, S1 and T1, are of pi,pi* origin, whereas for their precursors S1 is n,pi*, and T1 is pi,pi*. In both thienocarbazoles it appears that the thianaphthene ring dictates the S1 --> T1 yield, albeit there is less predominance of that ring in the triplet state of the linear thienocarbazole, which leads to a decrease in the observed phiT value.