Multifunctional hybrid materials based on transparent poly(methyl methacrylate) reinforced by lanthanoid hydroxo clusters

Three pentanuclear lanthanoid hydroxo clusters of composition [Ln(OH)(5)(abzm)(10)], where Ln = Eu, Tb, Ho and abzm = di(4-allyloxy)benzoylmethanide, have been prepared. The structures have been characterised by means of IR, Raman, elemental analyses and X-ray diffraction, showing a pyramidal square-based cluster core. The clusters (Tb and Ho) exhibit Curie-Weiss Law behaviour, displaying antiferromagnetic ordering at low temperatures. The emission properties of the Eu cluster demonstrate the abzm(-) ligand is an efficient antenna (λ(ex) = 420 nm) only for the sensitisation of Eu luminescence in the visible range, via energy transfer to the (5)D(0) state of the trivalent metal. The clusters have been reacted in the presence of methyl methacrylate and azobisisobutyronitrile to prepare reinforced polymers via radical polymerisation. The obtained materials exhibit swelling upon immersion into organic solvents up to ≈ 110% of their original size, in agreement with the presence of cluster-crosslinked polymeric chains. Also, no loss of transparency was observed in the preparation of the materials. The characteristic red emission of the Eu cluster in also retained in the polymeric material.     

Sub-1-micron mesoporous silica particles functionalized with cyclodextrin derivative for rapid enantioseparations on ultra-high pressure liquid chromatography

Mesoporous silica particles of relatively uniform sub-1-micron size (0.6-0.9 μm) were successfully prepared by a modified synthesis strategy and applied in chiral separation in an ultra-high pressure liquid chromatography system. These particles were prepared via a ternary surfactant system (Pluronic P123, F127 and hexadecyltrimethyl-ammonium bromide) and subsequently derivatized with perphenylcarbamoylated-β-cyclodextrin moieties. The mesoporous silica particles, despite their submicron size, enabled low back-pressure operation on an ultra-high pressure liquid chromatography system at a maximum flow rate of 2 ml/min. In addition, the particles possessed high surface area (480 m(2)/g) and thus afforded high cyclodextrin derivative loading (32 μmol/g), demonstrating rapid enantioseparation and good resolution of 6 basic and neutral racemates.     

5-HT1A receptor pharmacophores to screen for off-target activity of α1-adrenoceptor antagonists

The α₁-adrenoceptors (α₁-ARs), in particular the α_1A-AR subtype, are current therapeutic targets of choice for the treatment of urogenital conditions, such as benign prostatic hyperplasia (BPH). Due to the similarity between the transmembrane domains of the α₁-AR subtypes, and the serotonin receptor subtype 1A (5-HT_1A-R), currently used α₁-AR subtype-selective drugs to treat BPH display considerable off-target affinity for the 5-HT_1A-R, leading to side effects. We describe the construction and validation of pharmacophores for 5-HT_1A-R agonists and antagonists. Through the structural diversity of the training sets used in their development, these pharmacophores define the properties of a compound needed to bind to 5-HT_1A receptors. Using these and previously published pharmacophores in virtual screening and profiling, we have identified unique chemical compounds (hits) that fit the requirements to bind to our target, the α_1A-AR, selectively over the off-target, the 5-HT_1A-R. Selected hits have been obtained and their affinities for α_1A-AR, α_1B-AR and 5-HT_1A-R determined in radioligand binding assays, using membrane preparations which contain human receptors expressed individually. Three of the tested hits demonstrate statistically significant selectivity for α_1A-AR over 5-HT_1A-R. All seven tested hits bind to α_1A-AR, with two compounds displaying K _i values below 1 μM, and a further two K _i values of around 10 μM. The insights and knowledge gained through the development of the new 5-HT_1A-R pharmacophores will greatly aid in the design and synthesis of derivatives of our lead compound, and allow the generation of more efficacious and selective ligands.     

A 310-helix single turn enforced by crosslinking of lysines with 1,1′-ferrocenedicarboxylic acid

Prior work has shown that covalently linking the side chains of amino acids in the i and i+3 and i and i+4 positions in a peptide will enforce a helical conformation. In this work the ability of an organometallic entity to enforce a helical conformation in a peptide was explored. The tetrapeptide Boc-Lys-Ala-Val-Lys-NHCH₃ was prepared, then reacted with 1,1′-ferrocenedicarboxylic acid chloride. Reaction of the lysine side chain amines with the diacid chloride resulted in a metallacyclicpeptide (1) in which the two lysines are crosslinked via the ferrocene. The solution conformation of the metallacyclicpeptide (1) was studied using CD and NMR spectroscopy. The NMR methods employed were Karplus analysis of coupling constants, chemical shift changes of NH protons and ROESY data. The results show that the metallacyclicpeptide (1) adopts a single turn of the 3₁₀-helix conformation.     

The efficient synthesis of (3R,4R,5R)-3-amino-4,5-dimethyl-octanoic acid, a chiral β-amino acid with potent affinity for the α2δ protein

A chiral β-amino acid containing three contiguous chiral centers was synthesized efficiently in 11 steps, employing enantio-enriched β-ketoester as a key intermediate, via stereoselective catalytic hydrogenation of the corresponding enamide. Stereoselective 1,4-addition of a methyl group and protonation were key to the preparation of the desired acid 12. Mild and efficient reaction conditions were applied to the enamine formation and protection to avoid epimerization at C-4 of compounds 13 and 14. The final compound was found to display potent affinity for the α₂δ-protein that is a recognized drug target for the treatment of a variety of diseases.     

Determination of ion structures in structurally related compounds using precursor ion fingerprinting

Structurally-related alkaloids were analyzed by electrospray ionization/multiple stage mass spectrometry (ESI/MS ⁿ ) at varying collision energies to demonstrate a conceptual algorithm, precursor ion fingerprinting (PIF). PIF is a new approach for interpreting and library-searching ESI mass spectra predicated on the precursor ions of structurally-related compounds and their matching product ion spectra. Multiple-stage mass spectra were compiled and constructed into “spectral trees” that illustrated the compounds’ product ion spectra in their respective mass spectral stages. The precursor ions of these alkaloids were characterized and their spectral trees incorporated into an MS ⁿ library. These data will be used to construct a universal, searchable, and transferable library of MS ⁿ spectra. In addition, PIF will generate a proposed structural arrangement utilizing previously characterized ion structures, which will assist in the identification of unknown compounds.     

Evidence for the formation of anhydrous zinc acetate and acetic anhydride during the thermal degradation of zinc hydroxy acetate,Zn5(OH)8(CH3CO2)2·4H2O to ZnO

Zinc hydroxy acetate, Zn₅(OH)₈(CH₃CO₂)₂·4H₂O, has been prepared by the precipitation method. It has been demonstrated by FTIR analysis that, contrary to previous reports, the interaction of the acetate anion with the matrix cation is ionic. TG analysis, mass spectral analysis of the evolved gases, and in situ variable temperature PXRD and FTIR analysis have shown that decomposition of the material to ZnO involves the formation of Zn₅(OH)₈(CH₃CO₂), Zn₃(OH)₄(CH₃CO₂)₂ and anhydrous zinc acetate (Zn(CH₃CO₂)₂) as some of the acetate-containing intermediate solid products. The acetate anion is finally lost, at temperatures below 400 °C, as acetic anhydride, (CH₃CO)₂O.     

Spectral and biological studies of copper(II) complexes of 2-acetyl-pyridine thiosemicarbazones with bulky 4N-substituents

Summary Copper(II) complexes of a large number of 2-acetylpyridine ⁴N-alkyl thiosemicarbazones were prepared and characterized. I.r., electronic and e.s.r. spectra of the complexes, as well as ¹H and ¹³C n.m.r. spectra of the thiosemicarbazones, were obtained. Both the thiosemicarbazones and their complexes show either modest or no growth inhibitory activity against Aspergillus niger, but many have considerable activity against Paecilomyces variotii. There is a relationship between the antifungal activity and size of the ⁴N-substituent for both the thiosemicarbazones and their copper(II) complexes.     

Solution synthesis of germanium nanowires using a Ge2+ alkoxide precursor

A simple solution synthesis of germanium (Ge0) nanowires under mild conditions (<400 degrees C and 1 atm) was demonstrated using germanium 2,6-dibutylphenoxide, Ge(DBP)2 (1), as the precursor where DBP = 2,6-OC6H3(C(CH3)3)2. Compound 1, synthesized from Ge(NR2)2 where R = SiMe3 and 2 equiv of DBP-H, was characterized as a mononuclear species by single-crystal X-ray diffraction. Dissolution of 1 in oleylamine, followed by rapid injection into a 1-octadecene solution heated to 300 degrees C under an atmosphere of Ar, led to the formation of Ge0 nanowires. The Ge0 nanowires were characterized by transmission electron microscopy (TEM), X-ray diffraction analysis, and Fourier transform infrared spectroscopy. These characterizations revealed that the nanowires are single crystalline in the cubic phase and coated with oleylamine surfactant. We also observed that the nanowire length (0.1-10 microm) increases with increasing temperature (285-315 degrees C) and time (5-60 min). Two growth mechanisms are proposed based on the TEM images intermittently taken during the growth process as a function of time: (1) self-seeding mechanism where one of two overlapping nanowires serves as a seed, while the other continues to grow as a wire; and (2) self-assembly mechanism where an aggregate of small rods (<50 nm in diameter) recrystallizes on the tip of a longer wire, extending its length.