A new and efficient synthesis of N3-cycloalkylamino-6,8-diaminopurines

[Excerpt] The purine core is a privileged scaffold in medicinal chemistry and the biological relevance of purine derivatives makes them attractive targets in the preparation of combinatorial libraries.1,2 In particular, there is a great interest in the synthesis of 8-substituted purines due to their important potential as antiviral and anticancer agents.3 Reports on 8-aminopurines are limited and general methods to obtain these purine derivatives are still needed.4 Cyclic amines and hydrazines are key structural motifs in various bioactive agents.5 Here we report a novel, efficient and inexpensive method for the synthesis of 6,8-diaminopurines 4 incorporating cycloalkylamino substituents at N3position of the purine ring. (...)

Clinical Epidemiology of Buruli ulcer from Benin (2005-2013): effect of time-delay to diagnosis on clinical forms and severe phenotypes

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter =15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.

Assessment of the mechanical performance of recycled unbound materials for pavement subbase layers

The cyclic load triaxial test is a laboratory test that allows studying the mechanical behaviour of unbound granular materials used in base/subbase layers of road pavements. The resilient modulus and permanent strains are required as inputs in structural pavement design. This paper presents some results obtained for recycled materials (crushed concrete aggregate and blended crushed waste aggregate), with a view to promoting their use in pavement structures. Results relating to a reference material (limestone) are also presented, for comparison. All the test results discussed in this paper were obtained in variable cyclic radial pressure (VCP) tests. The tests performed (VCP) aim to study the influence of water content on the resilient modulus of recycled materials, as well as on the resistance to permanent deformation. Using the experimental data as a basis, further modelling work was carried out to establish the stresses developing in base/capping layers in typical Belgian road pavements. These numerical results allow to propose some simplifications of the stress paths applied in the testing procedures and to establish a new test protocol that also considers compaction during construction works. The results of this research work provide an excellent set of findings for the mechanical characterization of unbound base materials through the cyclic triaxial test, and contribute to a better understanding and correct application of recycled materials under geotechnical engineering background

Effect of the alkyl chain length of the ionic liquid anion on polymer electrolytes properties

New polymer electrolytes (PEs) based on chitosan and three ionic liquid (IL) families ([C2mim][CnSO3], [C2mim][CnSO4] and [C2mim][diCnPO4]) were synthesized by the solvent casting method. The effect of the length of the alkyl chain of the IL anion on the thermal, morphological and electrochemical properties of the PEs was studied. The solid polymer electrolytes (SPE) membranes were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), polarized optical microscopy (POM), atomic force microscopy (AFM), complex impedance spectroscopy (ionic conductivity) and cyclic voltammetry (CV). The obtained results evidenced an influence of the alkyl chain length of the IL anion on the temperature of degradation, birefringence, surface roughness and ionic conductivity of the membranes. The DSC, XRD and CV results showed independency from the length of the IL-anion-alkyl chain. The PEs displayed an predominantly amorphous morphology, a minimum temperature of degradation of 135 °C, a room temperature (T = 25 °C) ionic conductivity of 7.78 × 10−4 S cm−1 and a wide electrochemical window of ∼ 4.0 V.

Synthesis of five-membered heterocycles by indirect electrochemical approach in "Green" media

Radical cyclization continues to be a central methodology for the preparation of natural products containing heterocyclic rings. Hence, some electrochemical results obtained by cyclic voltammetry and controlled-potential electrolysis in the study of electroreductive intramolecular cyclization of ethyl (2S, 3R)-2-bromo-3-propargyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy) propanoate (1a), 2-bromo-3-allyloxy-3-(2’,3’,4’,6’-tetra-O-acetyl-beta-D-glucopyranosyloxy)propanoate (1b), 2-bromo-[1-(prop-2-yn-1-yloxy)propyl]benzene (1c) and [1-bromo-2-methoxy-2-(prop-2’-yn-1-yloxy)ethyl]benzene (1d) promoted by (1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane)nickel(I), [Ni(tmc)]+, electrogenerated at glassy carbon cathodes in ethanol and ethanol:water mixtures containing tetraalkylammonium salts, are presented. During controlled-potential electrolyses of solutions containing [Ni(tmc)]2+ and bromoalkoxylated compounds (1) catalytic reduction of the latter proceeds via one-electron cleavage of the carbon–bromine bond to form a radical intermediate that undergoes cyclization to afford the substituted tetrahydrofurans.

Electrosynthesis of heterocyclic compounds by radical cyclization in environmentally friendly media

We investigated the reductive intramolecular cyclization of bromopropargyl ethers derivatives, catalyzed by electrogenerated (1,4,8,11-tetramethyl-1,4,8,11-tetraaza-cyclotetradecane)nickel(I), [Ni(tmc)]+ as the catalysts in N,N,N-trimethyl-N-(2- hydroxyethyl)ammonium bis(trifluoromethylsulfonyl)imide,[N1 1 1 2(OH)][NTf2] and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C2mim][NTf2] by cyclic voltammetry and controlled-potential electrolysis. The results show that the reaction leads to the formation of the expected cyclic compounds, which are important intermediates in the synthesis of natural products with possible biological activities.

Polymer electrolytes for electrochromic devices

Polymer electrolytes are currently the focus of much attention as potential electrolytes in electrochemical devices such as batteries, display devices and sensors. Generically, solid polymer electrolytes (SPEs) are mixtures of salts with soft polar polymers. SPEs have many advantages including high energy density, no risk of leakage, no issues related to the presence of solvent, wide electrochemical stability windows, simplified processability and light weight. With the goal of developing a new family of environmentally friendly multifunctional biohybrid materials displaying high ionic conductivity we have produced in the present work, flexible films based on different polymers or hybrids incorporating different salts. The polymer electrolytes studied here have been characterized by means of Differential Scanning Calorimetry, Thermogravimetric Analysis, X-ray diffraction, Polarized Optical Microscopy, complex impedance spectroscopy and cyclic voltammetry. An evaluation of the performance of the sample with the highest conductivity as electrolyte in all solid-state ECDs was performed.

Laccase-catalyzed synthesis of conducting polyaniline-lignosulfonate composite

Enzymatic polymerization of aniline was first performed in lignosulfonate (LGS) template system. High-redox-potential catalyst laccase, isolated from Aspergillus, was used as a biocatalyst in the synthesis of conducting polyaniline/lignosulfonate (PANI-ES-LGS) complex using atmospheric oxygen as the oxidizing agent. The linear templates (LGS), also serving as the dopants, could facilitate the directional alignment of the monomer and improve the solubility of the conducting polymer. The process of the polymerization was monitored using UV-Vis spectroscopy, by which the conditions for laccase-catalyzed synthesis of PANI-ES-LGS complex were also optimized. The structure characterizations and solubility of the complex were carried out using corresponding characterization techniques respectively. The PANI-ES-LGS suspensions obtained was used as coating for cotton with a conventional padder to explore the applications of the complex. The variable optoelectronic properties of the coated cotton were confirmed by cyclic voltammetry and color strength test. The molecular weight changes of LGS treated by laccase were also studied to discuss the mechanism of laccase catalyzed aniline polymerization in LGS template system.

High-aspect-ratio tridimensional electrode arrays for neural applications

Tese de Doutoramento em Engenharia Biomédica.

Neurocognitive profile and cognitive intervention in Alzheimer's disease

Tese de Doutoramento em Psicologia (Especialidade de Psicologia Clínica)

Biomaterials for cartilage tissue engineering under mechanical stimulus

Tese de Doutoramento em Ciências (Especialidade de Física)