M. Alice Carvalho

In silico directed chemical probing of the adenosine receptor family

One of the grand challenges in chemical biology is identifying a small-molecule modulator for each individual function of all human proteins. Instead of targeting one protein at a time, an efficient approach to address this challenge is to target entire protein families by taking advantage of the relatively high levels of chemical promiscuity observed within certain boundaries of sequence phylogeny. We recently developed a computational approach to identifying the potential protein targets of compounds based on their similarity to known bioactive molecules for almost 700 targets. Here, we describe the direct identification of novel antagonists for all four adenosine receptor subtypes by applying our virtual profiling approach to a unique synthesis-driven chemical collection composed of 482 biologically-orphan molecules. These results illustrate the potential role of in silico target profiling to guide efficiently screening campaigns directed to discover new chemical probes for all members of a protein family.

Synthesis of novel 6-enaminopurines.

Two different approaches have been used for the synthesis of 6-enaminopurines 6 from 5-amino-4-cyanoformimidoyl imidazoles. In the first approach imidazoles 1 were reacted with ethoxymethylenemalononitrile or ethoxymethylenecyanoacetate under mild experimental conditions and this led to 9-substituted-6-(1-amino-2,2-dicyanovinyl) purines 6a-f or 9-substituted-6-(1-amino-2-cyano-2-methoxycarbonylvinyl) purines 6g-k. These reactions are postulated to occur through an imidazo-pyrrolidine intermediate 7, which rapidly rearranges to the 6-enaminopurine 6. In the second approach 6-methoxyformimidoyl purines 3, prepared in two efficient steps from 5-amino-4-cyanoformimidoyl imidazoles 1, were reacted with malononitrile and methylcyanoacetate with a mild acid catalysis (ammonium acetate or piperidinium acetate) to give 6-enaminopurines 6a, 6d, 6f, 6g and 6k in very good yields. Only low yields were obtained for the 6-enaminopurine 6j, as competing nucleophilic attack on C-8 of either 3d or 6jcauses ring opening with formation of pyrimido-pyrimidines 11 and 10a respectively.

Host(beta zeolite)–guest (copper(II)–methyladenine complex) nanomaterials: synthesis and characterization

The guest copper(II)–methyladenine complex was entrapped into beta zeolite (BEA) as a host by a process of sequential introduction of the components in the liquid phase followed by assembly inside the void space of the zeolite. The beta zeolite was prepared by an original technique. The appropriate process chosen for the in situ complex synthesis was using a 9-methyladenine ligand : copper(II) molar ratio of 4 : 1. The new host–guest nanomaterial was purified by Soxhlet extraction. The BEA zeolite with copper(II)–methyladenine complex was characterized by several techniques: SEM and XRD, chemical analysis (CA), spectroscopic methods (EPR, FTIR, UV-Vis and XPS) and TGA (thermal analysis). Analysis of the data indicates that the guest copper(II) complex was effectively immobilized in BEA without any modification of the morphology and structure of the zeolite. The coordination of the 9-methyladenine ligand with copper(II) ion as guest in the host nanomaterial was obtained with a preferential 1 : 1 stoichiometry.

Encapsulation of Cu(II) purine derivative complexes in NaY zeolite

The encapsulation of Cu(II) purine derivative complex was carried out by ion exchange of the complex from aqueous solutions into zeolite NaY. The entrapped complex was characterized by spectroscopic methods (FTIR and ICP-AES) and surface analysis (XRD). The various techniques of characterization used show that the Cu(II) complex was effectively encapsulated in the zeolite and this process does not modify the morphology and structure of the NaY zeolite. These materials have potential applications in heterogeneous catalysis in mild reaction conditions.

Synthesis and radical scavenging activity of phenol–imidazole conjugates

Novel hydroxylated benzylideneamino imidazole derivatives were synthesized and their radical scavenging activity was assessed against DPPH and hydroxyl radicals. In the DPPH assay, most of the synthesized compounds showed an IC50 in the range 3.2μM⩽IC50⩽8.4μM, lower than the reference compound trolox (IC50=9.5μM) or the parent aldehydes (5.4μM⩽IC50⩽11.6μM). The activity depends mainly on the phenolic subunit (number and position of the hydroxyl groups) and the extent of conjugation with the imidazole ring. In the deoxyribose assay, all the compounds, including parent imidazoles and aldehydes, showed high activity against the hydroxyl radical and the ability to chelate iron ions. At 5μM concentration, the compounds protected the deoxyribose from degradation by hydroxyl radical between 62% and 38%.

Sustainability and circular economy through PBL: Engineering students’ perceptions

This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundacao para a Ciencia e Tecnologia within the Project Scope: UID/CEC/00319/2013. The authors are also grateful to the students that participated in the PBL project.