Radiation grafting of glycidyl methacrylate onto cotton gauzes for functionalization with cyclodextrins and elution of antimicrobial agents

The aim of this work was to functionalize cotton gauzes with cyclodextrins in order to endow them with the ability to elute antimicrobial agents and to prevent infections. Gauzes were modified according to a two-steps approach: (1) pre-irradiation of the gauzes (Gammabeam) to graft glycidyl methacrylate (GMA), and (2) covalent binding of cyclodextrins (CDs) to the GMA-grafted gauzes. First the dependence of GMA grafting yield on the radiation dose (from 1 to 20 kGy) and the time of reaction was evaluated in detail. Anchorage of β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was confirmed by FTIR, TGA, and 3-methylbenzoic acid sorption. Differently from pristine gauzes, CD-functionalized GMA-grafted gauzes were able to load an anionic antibiotic drug, specifically nalidixic acid, and to sustain the release for 6 h. Drug-loaded gauzes were tested in vitro against E. coli and the results prove the suitability of the functionalization approach to efficiently inhibit the growth of this microorganism.     

Small molecule solar cells based on a series of water-soluble zinc phthalocyanine donors

Organic solar cells based on a series of water-soluble zinc phthalocyanines (wsZnPc) with varying numbers of sulfonate peripheral substituents and a C60 donor have been fabricated and characterised. We find that the number of substituents affects both the V(oc) and J(sc) of the devices, with the disulfonated wsZnPc devices performing best.     

Ligand effects on the dimensionality of oxamato-bridged mixed-metal open-framework magnets

Increasing dimensionality [from 2D (1) to 3D (2)] and T(C) [from 10 (1) to 20 K (2)] in two new oxamato-bridged heterobimetallic Mn(II)(2)Cu(II)(3) open-frameworks result from the steric hindrance provided by the different alkyl substituents of the N-phenyloxamate bridging ligands.     

Redox switching of the antiferromagnetic coupling in permethylated dicopper(II) paracyclophanes

A unique magnetic electroswitching behavior has been observed in an oxamato-based permethylated dicopper(II) paracyclophane; upon reversible one-electron oxidation of the double tetramethyl-substituted p-phenylenediamidate bridging skeleton, the spin alignment of the two Cu(II) ions (S(Cu) = ?) changes from antiparallel (OFF) to parallel (ON) in the resulting dicopper(II) π-radical cation species.     

QSAR modeling of endpoints for peptides which is based on representation of the molecular structure by a sequence of amino acids

The representation of the molecular structure by a system (sequence) of amino acids has been used to establish quantitative structure–property/activity relationships (QSPR/QSAR) which can be used for (i) bioactivities of epitope-peptides, (ii) antibacterial potencies of polypeptides, and (iii) the binding affinity of peptides that bind to the class I major histocompatibility complex molecule HLA-A*0201. The representation of the peptide structure has been done via 1-letter abbreviations of amino acids, i.e., A (alanine), C (cysteine), D (aspartic), etc. This approach allows classifying amino acids according to their function in a biochemical process (promoters of increase or decrease of an endpoint).     

Metabolomic study of plasma of patients with abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an important health problem, both because of AAA rupture and death and because of increased cardiovascular mortality. Identification of new biomarkers of AAA may suggest novel pathological mechanisms and targets for new medical treatments to slow AAA progression. Metabolic changes in AAA patients were mainly related to carbohydrate and lipid metabolism and many of these changes can be associated with a situation of insulin resistance (which can be related to metabolic syndrome) together with altered amino acid metabolism. For the first time, metabolites that can be associated with differential metabolism by the gut microflora of AAA patients have also been found. Moreover, aminomalonic acid in plasma has been shown to be the metabolite with the biggest difference between patients suffering from large aneurysm (>5 cm) and controls.     

Searching the "biologically relevant"conformation of dopamine: a computational approach

We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2-DR). A reduced 3D model for the binding pocket of the human D2-DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations. To obtain the different complexes of DA/D2-DR, we combined semiempirical (PM6), DFT (B3LYP/6-31G(d)), and QTAIM calculations. The molecular flexibility of DA interacting with the D2-DR was evaluated from potential energy surfaces and potential energy curves. A comparative study between the molecular flexibility of DA in the gas phase and at D2-DR was carried out. In addition, several molecular dynamics simulations were carried out to evaluate the molecular flexibility of the different complexes obtained. Our results allow us to postulate the complexes of type A as the "biologically relevant conformations" of DA. In addition, the theoretical calculations reported here suggested that a mechanistic stepwise process takes place for DA in which the protonated nitrogen group (in any conformation) acts as the anchoring portion, and this process is followed by a rapid rearrangement of the conformation allowing the interaction of the catecholic OH groups.     

Mimicking anaesthetic-receptor interaction: a combined spectroscopic and computational study of propofol···phenol

Propofol is a general anaesthetic that exerts its action by interaction with the GABA(A) receptor. Crystallographic studies suggest that there is a direct interaction between propofol and the phenolic residue of a tyrosine in the channel. In this study we create propofol···phenol clusters by their co-expansion in jets. The complex is probed using a set of mass-resolved spectroscopic strategies: 2-color REMPI, UV/UV hole-burning, IR/UV double resonance and the novel technique IR/IR/UV triple resonance. The existence of at least six different isomers in the expansion is demonstrated. All the isomers are stabilized by interactions between their aromatic rings. Additionally, in some conformers the OH moieties form hydrogen bonds in some of the isomers, with propofol and phenol alternating their donor-acceptor roles, while in others the -OH···OH angle points to a dipole-dipole interaction. Interpretation of the data in the light of dispersion-corrected DFT calculations shows that shallow barriers separate all the isomers, both in the ground and excited electronic states. Comparison of the structures of the complex with the X-ray diffraction data is also offered.     

Variation of the ground spin state in homo- and hetero-octanuclear copper(II) and nickel(II) double-star complexes with a meso-helicate-type metallacryptand core

Homo- and heterometallic octanuclear complexes of formula Na?{[Cu?(mpba)?][Cu(Me?dien)]?}-(ClO?)?·12H?O (1), Na?{[Cu?(Mempba)?][Cu(Me?dien)]?}(ClO?)?·12H?O (2), Na?{[Ni?(mpba)?]-[Cu(Me?dien)]?}(ClO?)?·12H?O (3), Na?{[Ni?(Mempba)?][Cu(Me?dien)]?}(ClO?)?·9H?O (4), {[Ni?(mpba)?][Ni(dipn)(H?O)]?}(ClO?)?·12.5H?O (5), and {[Ni?(Mempba)?][Ni(dipn)-(H?O)]?}(ClO?)?·12H?O (6) [mpba = 1,3-phenylenebis(oxamate), Mempba = 4-methyl-1,3-phenylenebis(oxamate), Me?dien = N,N,N',N',N'-pentamethyldiethylenetriamine, and dipn = dipropylenetriamine] have been synthesized through the "complex-as-ligand/complex-as-metal" strategy. Single-crystal X-ray diffraction analyses of 1, 3, and 5 show cationic M(II)?M'(II)? entities (M, M' = Cu and Ni) with an overall double-star architecture, which is made up of two oxamato-bridged M(II)M'(II)? star units connected through three meta-phenylenediamidate bridges between the two central metal atoms leading to a binuclear metallacryptand core of the meso-helicate-type. Dc magnetic susceptibility data for 1-6 in the temperature range 2-300 K have been analyzed through a "dimer-of-tetramers" model [H = - J(S(1A)·S(3A) + S(1A)·S(4A) + S(1A)·S(5A) + S(2B)·S(6B) + S(2B)·S(7B) + S(2B)·S(8B)) - J'S(1A)·S(2B), with S(1A) = S(2B) = S(M) and S(3A) = S(4A) = S(5A) = S(6B) = S(7B) = S(8B) = S(M')]. The moderate to strong antiferromagnetic coupling between the M(II) and M'(II) ions through the oxamate bridge in 1-6 (-J(Cu-Cu) = 52.0-57.0 cm?1, -J(Ni-Cu) = 39.1-44.7 cm?1, and -J(Ni-Ni) = 26.3-26.6 cm?1) leads to a non-compensation of the ground spin state for the tetranuclear M(II)M'(II)? star units [S(A) = S(B) = 3S(M') - S(M) = 1 (1 and 2), 1/2 (3 and 4), and 2 (5 and 6)]. Within the binuclear M(II)? meso-helicate cores of 1-4, a moderate to weak antiferromagnetic coupling between the M(II) ions (-J'(Cu-Cu) = 28.0-48.0 cm?1 and -J'(Ni-Ni) = 0.16-0.97 cm?1) is mediated by the triple m-phenylenediamidate bridge to give a ground spin singlet (S = S(A) - S(B) = 0) state for the octanuclear M(II)?Cu(II)? molecule. Instead, a weak ferromagnetic coupling between the Ni(II) ions (J'(Ni-Ni) = 2.07-3.06 cm?1) operates in the binuclear Ni(II)? meso-helicate core of 5 and 6 leading thus to a ground spin nonet (S = S(A) + S(B) = 4) state for the octanuclear Ni(II)? molecule. Dc magnetization data for 5 reveal a small but non-negligible axial magnetic anisotropy (D = -0.23 cm?1) of the S = 4 Ni(II)? ground state with an estimated value of the energy barrier for magnetization reversal of 3.7 cm?1 (U = -DS2). Ac magnetic susceptibility data for 5 show an unusual slow magnetic relaxation behaviour at low temperatures which is typical of "cluster glasses". The temperature dependence of the relaxation time for 5 has been interpreted on the basis of the Vogel-Fulcher law for weakly interacting clusters, with values of 2.5 K, 1.4 × 10?? s, and 4.0 cm?1 for the intermolecular interaction parameter (T?), the pre-exponential factor (τ?), and the effective energy barrier (U(eff)), respectively.     

Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants

We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.