A density functional theory computational study of the role of ligand on the stability of CuI and CuII species associated with ATRP and SET‐LRP

Atom transfer radical polymerization (ATRP) and single electron‐transfer living radical polymerization (SET‐LRP) both utilize copper complexes of various oxidation states with N‐ligands to perform their respective activation and deactivation steps. Herein, we utilize DFT (B3YLP) methods to determine the preferred ligand‐binding geometries for Cu/N‐ligand complexes related to ATRP and SET‐LRP. We find that those ligands capable of achieving tetrahedral complexes with Cu^I and trigonal bipyramidal with axial halide complexes with [Cu^IIX]⁺ have higher energies of stabilization. We were able to correlate calculated preferential stabilization of [Cu^IIX]⁺ with those ligands that perform best in SET‐LRP. A crude calculation of energy of disproportionation revealed that the same preferential binding of [Cu^IIX]⁺ results in increased propensity for disproportionation. Finally, by examining the relative energies of the basic steps of ATRP and SET‐LRP, we were able to rationalize the transition from the ATRP mechanism to the SET‐LRP mechanism as we transition from typical nonpolar ATRP solvents to polar SET‐LRP solvents. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4950–4964, 2007     

Mechanistic implications for the formation of the diiron cluster in ribonucleotide reductase provided by quantitative EPR spectroscopy

The small subunit of Escherichia coli ribonucleotide reductase (R2) is a homodimeric (betabeta) protein, in which each beta-peptide contains a diiron cluster composed of two inequivalent iron sites. R2 is capable of reductively activating O(2) to produce a stable tyrosine radical (Y122*), which is essential for production of deoxyribonucleotides on the larger R1 subunit. In this work, the paramagnetic Mn(II) ion is used as a spectroscopic probe to characterize the assembly of the R2 site with EPR spectroscopy. Upon titration of Mn(II) into samples of apoR2, we have been able to quantitatively follow three species (aquaMn(II), mononuclear Mn(II)R2, and dinuclear Mn(2)(II)R2) and fit each to a sequential two binding site model. As previously observed for Fe(II) binding within apoR2, one of the sites has a greater binding affinity relative to the other, K(1) = (5.5 +/- 1.1) x 10(5) M(-)(1) and K(2) = (3.9 +/- 0.6) x 10(4) M(-)(1), which are assigned to the B and A sites, respectively. In multiple titrations, only one dinuclear Mn(2)(II)R2 site was created per homodimer of R2, indicating that only one of the two beta-peptides of R2 is capable of binding Mn(II) following addition of Mn(II) to apoR2. Under anaerobic conditions, addition of only 2 equiv of Fe(II) to R2 (Fe(2)(II)R2) completely prevented the formation of any bound MnR2 species. Upon reaction of this sample with O(2) in the presence of Mn(II), both Y122* and Mn(2)(II)R2 were produced in equal amounts. Previous stopped-flow absorption spectroscopy studies have indicated that apoR2 undergoes a protein conformational change upon binding of metal (Tong et al. J. Am. Chem. Soc. 1996, 118, 2107-2108). On the basis of these observations, we propose a model for R2 metal incorporation that invokes an allosteric interaction between the two beta-peptides of R2. Upon binding the first equiv of metal to a beta-peptide (beta(I)), the aforementioned protein conformational change prevents metal binding in the adjacent beta-peptide (beta(II)) approximately 25 A away. Furthermore, we show that metal incorporation into beta(II) occurs only during the O(2) activation chemistry of the beta(I)-peptide. This is the first direct evidence of an allosteric interaction between the two beta-peptides of R2. Furthermore, this model can explain the generally observed low Fe occupancy of R2. We also demonstrate that metal uptake and this newly observed allosteric effect are buffer dependent. Higher levels of glycerol cause loss of the allosteric effect. Reductive cycling of samples in the presence of Mn(II) produced a novel mixed metal Fe(III)Mn(III)R2 species within the active site of R2. The magnitude of the exchange coupling (J) determined for both the Mn(2)(II)R2 and Fe(III)Mn(III)R2 species was determined to be -1.8 +/- 0.3 and -18 +/- 3 cm(-)(1), respectively. Quantitative spectral simulations for the Fe(III)Mn(III)R2 and mononuclear Mn(II)R2 species are provided. This work represents the first instance where both X- and Q-band simulations of perpendicular and parallel mode spectra were used to quantitatively predict the concentration of a protein bound mononuclear Mn(II) species.     

Polybrominated diphenyl ethers from Dysidea herbacea,Dysidea chlorea and Phyllospongia foliascens

The marine sponges Dysidea herbacea, D. chlorea and Phyllospongia foliascens were differentiated with difficulty in the field. D. herbacea contained 2-(2',4'-dibromophenoxy)-3,4,5-tribromophenol (1), 2-(2',4'-dibromophenoxy)-4,5,6-tribromophenol (2) and 2-(2',4'-dibromophenoxy)-3,5-dibromophenol (6). D. chlorea contained only 2-(2',4'-dibromophenoxy)-4,6-dibromophenol(3), a compound previously reported as a metabolite of D. herbacea. Phyllospongia foliascens contained 2-(3',5'-dibromo-2'-methoxy-phenoxy)-3,5-dibromoanisole (7) and a 1:2 mixture of 2-(3',5'-dibromo-2'-hydroxyphenoxy)-3,5,6-tribromophenol (8) and 2-(3',5'-dibromo-2'-hydroxyphenoxy)-3,4,5,6-tetrabromophenol (9).     

In situ tissue pathology from spatially encoded mass spectrometry classifiers visualized in real time through augmented reality

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data. Spatially encoded pathology classifications are displayed at the site of laser sampling as color-coded pixels in an augmented reality video feed of the surgical field of view. This is enabled by two-way communication between surgical navigation and mass spectrometry data analysis platforms through a custom-built interface. Performance of the system was evaluated using murine models of human cancers sampled in situ in the presence of body fluids with a technical pixel error of 1.0 ± 0.2 mm, suggesting a 84% or 92% (excluding one outlier) cancer type classification rate across different molecular models that distinguish cell-lines of each class of breast, brain, head and neck murine models. Further, through end-point immunohistochemical staining for DNA damage, cell death and neuronal viability, spatially encoded PIRL-MS sampling is shown to produce classifiable mass spectral data from living murine brain tissue, with levels of neuronal damage that are comparable to those induced by a surgical scalpel. This highlights the potential of spatially encoded PIRL-MS analysis for in vivo use during neurosurgical applications of cancer type determination or point-sampling in vivo tissue during tumor bed examination to assess cancer removal. The interface developed herein for the analysis and the display of spatially encoded PIRL-MS data can be adapted to other hand-held mass spectrometry analysis probes currently available.

Integration between a hand-held mass spectrometry desorption probe based on picosecond infrared laser technology (PIRL-MS) and an optical surgical tracking system demonstrates in situ tissue pathology from point-sampled mass spectrometry data.     

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.     

Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry

A series of isobaric disaccharide-alditols, four derived from O-linked glycoproteins, and select trisaccharides were rapidly resolved using tandem high resolution atmospheric pressure ion-mobility time-of-flight mass spectrometry. Electrospray ionization was used to create the gas-phase sodium adducts of each carbohydrate. Using this technique it was possible to separate up to three isobaric disaccharide alditols and three trisaccharides in the gas phase. Reduced mobility values and experimentally determined ion-neutral cross sections are reported for each sodium-carbohydrate complex. These studies demonstrated that ion mobility separations at atmospheric pressure can provide a high-resolution dimension for analysis of carbohydrate ions that is complementary to traditional mass spectral (m/z) ion analysis. Combining these independent principles for separation of ions provides a powerful new bioanalytical tool for the identification of isomeric carbohydrates.     

Asymmetric synthesis of beta-amino carbonyl compounds with N-sulfinyl beta-amino Weinreb amides

[reaction: see text] Diverse organometallic reagents readily add to enantiopure N-sulfinyl beta-amino Weinreb amides providing the corresponding, stable, N-sulfinyl beta-amino carbonyl compounds in good to excellent yields. This new methodology represents a general solution to the problem of beta-amino carbonyl syntheses, which are important chiral building blocks and constituents of natural products. N-Sulfinyl beta-amino Weinreb amides are prepared by reaction of the potassium enolate of N-methoxy N-methylacetamide with sulfinimines (N-sulfinyl imines) or lithium N,O-dimethylhydroxylamine with N-sulfinyl beta-amino esters.     

N-sulfinyl beta-amino Weinreb amides: synthesis of enantiopure beta-amino carbonyl compounds. Asymmetric synthesis of (+)-sedridine and (-)-allosedridine

[reaction: see text] N-Sulfinyl beta-amino Weinreb amides are prepared by condensation of sulfinimines with the potassium enolate of N-methoxy-N-methylacetamide. These new chiral building blocks are useful for the asymmetric synthesis of beta-amino carbonyl compounds, as illustrated here by the concise enantioselective syntheses of sedum alkaloids (+)-sedridine and (-)-allosedridine.     

Synthesis of the C11-C29 fragment of amphidinolide F

[reaction: see text] An efficient synthesis of the C(11)-C(29) fragment 31 of amphidinolide F has been accomplished via a diastereoselective [3 + 2]-annulation reaction of allylsilane 5 and ethyl glyoxylate to prepare the key tetrahydrofuran 15 and a highly stereoselective methyl ketone aldol reaction to generate the C(11)-C(16) segment.