Hydroboration with pyridine borane at room temperature

Treatment of pyridine borane (Py.BH3) with iodine, bromine, or strong acids affords activated Py.BH2X complexes that are capable of hydroborating alkenes at room temperature. Evidence is presented for an unusual hydroboration mechanism involving leaving group displacement. In contrast to THF.BH3, hydroboration with Py.BH2I selectively affords the monoadducts. The crude hydroboration products are converted into synthetically useful potassium alkyltrifluoroborate salts upon treatment with methanolic KHF2.     

An effective method for the discrimination of motional anisotropy and chemical exchange

Analysis of the ratio of transverse and longitudinal relaxation rates (R2/R1) is an approach commonly used for estimation of overall correlation time and identification of chemical exchange in biological macromolecules. However, this analysis fails to distinguish between chemical exchange and motional anisotropy. We describe a simple method for identifying chemical exchange and motional anisotropy using the product, R1R2. In the slow tumbling regime, the R1R2 product results in a constant value that is independent of overall correlation time and motional anisotropy. This analysis provides a simple method for rapidly estimating and dissociating the effects of motional anisotropy and chemical exchange in NMR heteronuclear spin relaxation data. We demonstrate the utility of the method with 15N relaxation data collected on the proteins E. coli ribonuclease H and the trimeric E. coli membrane associated lipoprotein lpp.     

Spongistatin synthetic studies. An efficient, second-generation construction of an advanced ABCD intermediate

[reaction: see text] A short, efficient, and stereocontrolled synthesis of (-)-4, an advanced ABCD subunit of the spongistatins, has been achieved. Central to the synthetic strategy is the multicomponent linchpin union of silyl dithianes with epoxides to access both the AB and CD fragments. Fragment coupling was then achieved via an efficient stereoselective aldol reaction. The linear sequence required 22 steps and proceeded in 4.0% overall yield.     

NEW PHTHALOCYANINE PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

Six new aluminum and silicon phthalocyanines have been synthesized and their photocytotoxicity toward V79 cells has been studied. The compounds that have been prepared are: AIPcOSi(CH₃)₂(CH₂),N(CH₃)₂, I; AIPcOSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?, II; CH₃SiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, III; HOSiPcOSi(CH₃)₂(CH₂)₃N(CH₃)₂, IV; HOSiPcOSi(CH₃)₂(CH₂)₃)₃(CH₃)₃⁺I^?, V; and SiPc[OSi(CH₃)₂(CH₂)₃N(CH₃)₃⁺I^?]₂, VI. Relative growth delay values for compounds I-VI and relative cytotoxicity values for compounds I, II, IV, V and VI have been determined. Compounds I and II have been shown to be comparable in photocytotoxicity to what is presumed to be AIPcOH.xH₂O, and compound IV has been shown to have greater activity. The classes of compounds to which these six compounds belong appear to have potential for photodynamic therapy.     

DNA LESIONS AND DNA DEGRADATION IN MOUSE LYMPHOMA L5178Y CELLS AFTER PHOTODYNAMIC TREATMENT SENSITIZED BY CHLOROALUMINUM PHTHALOCYANINE

Two closely related strains of mouse lymphoma L5178Y cells, LY-R and LY-S, have been found to differ in their sensitivity to the cytotoxic effects of photodynamic treatment (PDT) with chloroaluminum phthalocyanine (CAPC) and red light. Strain LY-R is more sensitive to photodynamic cell killing than strain LY-S. Differences in uptake of CAPC could not account for the differences in cytotoxic effects. There was no marked difference between the two strains in the induction of single-strand breaks (which includes frank single-strand breaks and alkali-labile lesions), but substantially more DNA-protein cross-links were formed in strain LY-R by CAPC and light. Repair of single-strand breaks proceeded with similar kinetics in both strains for the first 30 min post-irradiation, suggesting that these lesions are not responsible for the differential sensitivity of the two strains to the lethal effects of photodynamic treatment. Thereafter, alkaline elution revealed the presence of increasing DNA strand breakage in strain LY-R. DNA degradation, as measured by the conversion of prelabeled [14C] DNA to acid-soluble radioactivity, was more rapid and extensive in strain LY-R.     

Capillary-channeled polymer fibers as stationary phases in liquid chromatography separations

A method utilizing capillary-channeled polymer (C-CP) fibers as stationary phases in high-performance liquid chromatographic separations has been investigated. Polymeric fibers of differing backbones (polypropylene and polyester) having nominal diameters of approximately 50 and approximately 35 microm and a channeled structure on their periphery were packed into stainless steel tubing (305 x 4.6 mm I.D.) for use in reversed-phase separations of various mixtures. The fibers have eight channels running continuously along the axis which exhibit very high surface activity. As such, solvent transport is affected through the channels through wicking action. Bundles of 1000-3000 fibers are loaded co-linearly into the tubing, providing flow channels extending the entire length of the columns. As a result, backing pressures are significantly lowered (approximately 50% reduction) in comparison to packed-sphere columns. In addition, the capital costs of the fiber material (< US$0.25 per column) are very attractive. Flow-rates of up to 5 ml/min can be used to achieve near baseline separation of related compounds in reasonable run times, indicating very fast mobile phase mass transfer (C-terms). The polymer stationary phases demonstrate high selectivity for a wide variety of analytes with gradient elution employed successfully in many instances. Specifically, separations of three polyaromatic hydrocarbons (benzo[a]pyrene, chrysene, pyrene), mixtures of both organic and inorganic lead compounds [chlorotriethyllead, chlorotriphenyllead, lead nitrate, lead(II) phthalocyanine], and a lipid standard of triglycerides were accomplished on the polymeric stationary phases. Other species of biological interest, including groups of aliphatic and aromatic amino acids have also been effectively separated. The reversed-phase nature of the fiber surfaces is supported through atomic force microscopy measurements using hydrophilic and hydrophobic functionalized polystyrene beads as the probe tips. Separations of the various analytes demonstrate the feasibility of utilizing C-CP fibers as stationary phases in reversed-phase LC. It is envisioned that columns of this nature would be particularly useful in prep-scale separations as well as for immobilization matrices for organic constituents in aqueous environments.