Comparison of micro- and mesoporous inorganic materials in the uptake and release of the drug model fluorescein and its analogues

The uptake of the three species of the drug model fluorescein (fluorescein sodium salt (FNa), fluorescein free acid (F), and fluorescein diacetate (FDA)) by zeolite NaX and the mesoporous zeotype MCM-41 was investigated as well as their release rates into solutions at pH 7 and pH 4.5. UV/Vis analysis was carried out at a wavelength of 490 nm. Uptakes of the sodium salt of 9 % for zeolite X and 14 % for MCM suggest little penetration of the pores. The use of ethanol as the loading solvent for F resulted in little uptake for both zeolitic materials due to the successful competition of the ethanol for binding sites. Use of acetone (weaker proton acceptor) as loading solvent significantly improved the uptake of F to 17 % and 12 % for zeolite X and MCM, respectively, whilst the uptake of FDA in acetone increased still further to 22 % and 17 % for zeolite X and MCM, respectively. Generally there was a large initial release of the fluorescein analogues from the surface of the zeolites with very little further increase over time. The prescence of an esterase enzyme in the release medium of FDA tripled the release from MCM to 15 % but left the release from zeolite X unaffected at 6 %. The results obtained show that uptake of fluorescein and its analogues is dependent on the loading solvent used, the amount released is influenced by not only the solvent but the pH and the presence of enzymes in the release medium.     

Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai

[structure: see text] Two approaches to the synthesis of the aglycon 120 of polycavernoside A (1) were developed, only one of which was completed. The successful "second-generation" route assembled the aglycon seco acids 102 and 106 via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3-hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71. The latter was obtained from a sequence which commenced from the silyl ether 24 of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-zeta-hydroxy-alpha,beta-unsaturated ester 82. Regioselective Yamaguchi lactonization of trihydroxycarboxylic acids 102 and 106 and subsequent functional-group adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside moiety was attached. Stille coupling of the glycosidated aglycon 128 with dienylstannane 129 furnished polycavernoside A in a synthesis for which the longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.     

Growth dynamics and intracluster reactions in Ni+(CO2)n complexes via infrared spectroscopy

Ni(+)(CO(2))(n), Ni(+)(CO(2))(n)Ar, Ni(+)(CO(2))(n)Ne, and Ni(+)(O(2))(CO(2))(n) complexes are generated by laser vaporization in a pulsed supersonic expansion. The complexes are mass-selected in a reflectron time-of-flight mass spectrometer and studied by infrared resonance-enhanced photodissociation (IR-REPD) spectroscopy. Photofragmentation proceeds exclusively through the loss of intact CO(2) molecules from Ni(+)(CO(2))(n) and Ni(+)(O(2))(CO(2))(n) complexes, and by elimination of the noble gas atom from Ni(+)(CO(2))(n)Ar and Ni(+)(CO(2))(n)Ne. Vibrational resonances are identified and assigned in the region of the asymmetric stretch of CO(2). Small complexes have resonances that are blueshifted from the asymmetric stretch of free CO(2), consistent with structures having linear Ni(+)-O=C=O configurations. Fragmentation of larger Ni(+)(CO(2))(n) clusters terminates at the size of n=4, and new vibrational bands assigned to external ligands are observed for n> or =5. These combined observations indicate that the coordination number for CO(2) molecules around Ni(+) is exactly four. Trends in the loss channels and spectra of Ni(+)(O(2))(CO(2))(n) clusters suggest that each oxygen atom occupies a different coordination site around a four-coordinate metal ion in these complexes. The spectra of larger Ni(+)(CO(2))(n) clusters provide evidence for an intracluster insertion reaction assisted by solvation, producing a metal oxide-carbonyl species as the reaction product.     

Total synthesis of (-)-dysibetaine via a nitrenium ion cyclization-dienone cleavage strategy

The diastereoselective total synthesis of the marine natural product (-)-dysibetaine is reported. The key steps in this venture are i) a diastereoselective nitrenium ion spirocyclization, which serves to generate the pyrrolidinone ring and quaternary stereocenter of the target, and ii) use of the 2-methoxycyclohexa-2,5-dienone ring formed during cyclization as a masked 2-amino-1,3-dicarbonyl synthon.     

Size-selected (2-10 nm) gold nanoparticles for matrix assisted laser desorption ionization of peptides

In this report, first use of size-selected gold nanoparticles (AuNPs) as matrixes for matrix assisted laser desorption/ionization (MALDI) is described for peptides and proteins. In comparison with conventional organic acid MALDI matrixes, the optimum matrix-to-analyte ratio with AuNP matrixes is reduced by 10-14 orders of magnitude. Significant differences in the relative abundances of the ions observed in positive and negative mode MALDI-time-of-flight mass spectrometry (TOFMS) are revealed as the AuNP size distribution is decreased from 10 to 2 nm, whereby 2-nm AuNPs exhibit quantum confinement effects prevalent in quantum dots. AuNP matrixes allow for selective analyte ionization, as demonstrated in the selective MALDI-TOFMS of phosphotyrosine in a background of phosphoserine and phosphothreonine peptides.     

The Bohlmann-Rahtz route to functionalised pyridine scaffolds and their use in library synthesis

The Bohlmann-Rahtz reaction has been used to prepare 2,3,6-trisubstituted pyridines suitable for use in library synthesis. The synthesis of piperidine substituted nicotinic acid derivative 9 has been optimised and carried out on a large scale to give ca. 500 g of scaffold which was used in the generation of the pyridine library 11.     

The photolysis of platinacycloalkanes in solution

The photolysis of [I₂$\text{PtCH}{}_2\text{CH}{}_2\text{CH}{}_2\text{C}$H₂ (PMe₂ Ph)₂] gives ethylene and but-1-ene as volatile products, the latter probably being formed via a five-coordinate platinum intermediate. However, the formation of propene from the photolysis of [Cl₂$\text{PtCH}{}_2\text{CH}{}_2\text{C}$H₂ (1,10-phenanthroline) appears to involve a direct transfer of a hydrogen atom between neighbouring CH₂ groups in the ring. Other gaseous products, e.g. cyclopropane, ethylene, may be formed via a platinum ion radical.     

Reaction of tris(trimethylsilyl)methylsilicon halides with methanolic sodium methoxide. Probability of sila-olefin intermediates

The compounds TsiSiR₂X [Tsi = Me₃Si)₃C; R = Me, X = Cl, Br, I, or R = Ph, X = F, Cl, Br, I)] react with boiling 2 M MeONa-MeOH to give products of the type (Me₃Si)₂CHSiR₂OMe. It is suggested that the reaction proceeds through an elimination, analogous to E2 eliminations of alkyl halides, involving synchronous attack of MeO^? at an Me₃Si group, liberation of X^?, and formation of (Me₃Si)₂CSiR₂. The compounds TsiSiPhMeF TsiSiPhCl₂ react analogously to give (Me₃Si)₂CHSiPhMe(OMe) and (Me₃Si)₂CHSiPh(OMe)₂ [tha latter presumably by solvolysis of the initially-formed (Me₃Si)₂CHSiPhCl(OMe)]. The compounds TsiSiMe₂OMe and TsiSiMe₃ do not react, while TsiSiMe₂H gives TsiH. The compound TsiSiCl₃ reacts with 0.1 M MeONa-MeOH to give the substitution and elmination products TsiSiCl₂(OMe) and (Me₃Si)₂CHSi(OMe)₃ in ca. $\text{1}\text{2}$ ratio.