Synthesis of benzo[f]isoindole-4,9-diones

A synthesis of benzo[f]isoindole-4,9-diones 1 is presented starting from the reaction of 2,3-bis(bromomethyl)-1,4-dimethoxynaphthalene 15 with primary amines affording 2,3-bis(aminomethyl)-1,4-dimethoxynaphthalenes 14, which could be converted by CAN-mediated oxidation in one step to benzo[f]isoindole-4,9-diones 1. An alternative synthesis of benzo[f]isoindole-4,9-diones 1 starts from 2,3-bis(bromomethyl)-1,4-naphthoquinone 9 via 2,3-dihydrobenzo[f]isoindoles 10 which spontaneously oxidize.     

Charge-transfer and spin dynamics in DNA hairpin conjugates with perylenediimide as a base-pair surrogate

A perylenediimide chromophore (P) was incorporated into DNA hairpins as a base-pair surrogate to prevent the self-aggregation of P that is typical when it is used as the hairpin linker. The photoinduced charge-transfer and spin dynamics of these hairpins were studied using femtosecond transient absorption spectroscopy and time-resolved EPR spectroscopy (TREPR). P is a photooxidant that is sufficiently powerful to quantitatively inject holes into adjacent adenine (A) and guanine (G) nucleobases. The charge-transfer dynamics observed following hole injection from P into the A-tract of the DNA hairpins is consistent with formation of a polaron involving an estimated 3-4 A bases. Trapping of the (A 3-4) (+*) polaron by a G base at the opposite end of the A-tract from P is competitive with charge recombination of the polaron and P (-*) only at short P-G distances. In a hairpin having 3 A-T base pairs between P and G ( 4G), the radical ion pair that results from trapping of the hole by G is spin-correlated and displays TREPR spectra at 295 and 85 K that are consistent with its formation from (1*)P by the radical-pair intersystem crossing mechanism. Charge recombination is spin-selective and produces (3*)P, which at 85 K exhibits a spin-polarized TREPR spectrum that is diagnostic of its origin from the spin-correlated radical ion pair. Interestingly, in a hairpin having no G bases ( 0G), TREPR spectra at 85 K revealed a spin-correlated radical pair with a dipolar interaction identical to that of 4G, implying that the A-base in the fourth A-T base pair away from the P chromophore serves as a hole trap. Our data suggest that hole injection and transport in these hairpins is completely dominated by polaron generation and movement to a trap site rather than by superexchange. On the other hand, the barrier for charge injection from G (+*) back onto the A-T base pairs is strongly activated, so charge recombination from G (or even A trap sites at 85 K) most likely proceeds by a superexchange mechanism.     

The role of monomers and dimers in the reduction of ruthenium(II) complexes of redox-active tetraazatetrapyridopentacene ligand

A combination of electrochemistry, spectroelectrochemistry, and 1H NMR has been used to study the reduction and solution speciation in acetonitrile of two mononuclear Ru complexes containing the redox-active 9,11,20,22-tetraazatetrapyrido [3,2-a:2',3'-c:3' ',2' '-l:2' ',3' '-n]pentacene (tatpp) ligand. These complexes, [(bpy)2Ru(tatpp)][PF6]2 (1[PF6]2), and [(phen)2Ru(tatpp)][PF6]2 (2[PF6]2) (where bpy is 2,2'-bipyridine and phen is 1,10-phenanthroline), form pi-pi stacked dimers (e.g., pi-{1}24+ and pi-{2}24+) in solution as determined by 1H NMR studies in an extended concentration range (90 - 5000 microM) as well as via simulation of the electrochemical data. The dimerization constant for 12+ in acetonitrile is 2 x 10(4) M(-1) as determined from the NMR data. Slightly higher dimerization constants (8 x 10(4) M(-1)) were obtained via simulation of the electrochemical data and are attributed to the presence of the supporting eletrolyte. Electrochemical and spectroelectrochemical data show that the pi-pi stacked dimers are electroreduced in two consecutive steps at -0.31 and -0.47 V vs Ag/AgCl, which is assigned to the uptake of one electron by each tatpp ligand in pi-{1}24+ to give first pi-{1}23+and then pi-{1}22+. At potentials negative of -0.6 V, the electrochemical data reveal two different reaction pathways depending on the complex concentration in solution. At low concentrations (< or =20 microM), the next electroreduction occurs on a monomeric species (e.g., [(bpy)2Ru(tatpp)]+/0) showing that the doubly reduced pi-pi dimer (pi-{1}22+ and pi-{2}22+) dissociates into monomers. At high concentrations (> or =100 microM), reduction of pi-{1}22+ or pi-{2}22+ induces another dimerization reaction, which we attribute to the formation of a sigma-bond between the radical tatpp ligands and is accompanied by the appearance of a new peak in the absorption spectrum at 535 nm. This new sigma-dimer can undergo one additional tatpp based reduction to form sigma-{1}20 or sigma-{2}20, in which the tatpp-bridged assembly is the site of all four reductions. Finally, potentials negative of -1.2 V result in the electroreduction of the bpy or phen ligands for complexes 12+ or 22+, respectively. For the latter complex 22+, this process is accompanied by the formation of an electrode adsorbed species.     

Superoxide radical anion adduct of 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 3. Effect of mildly acidic pH on the thermodynamics and kinetics of adduct formation

The nitrone, 5,5-dimethylpyrroline N-oxide (DMPO), is a commonly used spin trap for the detection of superoxide radical anion (O2*-) using electron paramagnetic resonance spectroscopy. This work investigates the reactivity of DMPO to O2*- in mildly acidic pH (5.0-7.0). Mild acidity is characteristic of acidosis and has been observed in hypoxic systems, e.g., ischemic organs and cancer cells. Although the established pKa for O2*- is 4.8, the pKa for DMPO is unknown. The pKa of the conjugate acid of DMPO was determined to be 6.0 using potentiometric, spectrophotometric, 1H and 13C NMR, and computational methods. 1H and 13C NMR were employed to investigate the site of protonation. An alternative mechanism for the spin trapping of O2*- in mildly acidic pH was proposed, which involves protonation of the oxygen to form the N-hydroxy imino cation and subsequent addition of O2*-. The exoergicity of O2*- addition to protonated DMPO was rationalized using density functional theory (DFT) at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory.     

Correction of pre-steady-state KIEs for isotopic impurities and the consequences of kinetic isotope fractionation

We show, both experimentally and by kinetic modeling, that enzymatic single-turnover (pre-steady-state) H-transfer reactions can be significantly complicated by kinetic isotope fractionation. This fractionation results in the formation of more protiated than deuterated product and is a unique problem for pre-steady-state reactions. When observed rate constants are measured using rapid-mixing (e.g., stopped flow) methodologies, kinetic isotope fractionation can lead to a large underestimation of both the magnitude and temperature dependence of kinetic isotope effects (KIEs). This fractionation is related to the isotopic purity of the substrates used and highlights a major problem with experimental studies which measure KIEs with substrates that are not isotopically pure. As it is not always possible to prepare isotopically pure substrates, we describe two general methods for the correction, for known isotope impurities, of KIEs calculated from pre-steady-state measurements.     

Remote substituent effects upon the rearrangements of housane cation radicals

The rearrangement of a series of housane-derived cation radicals was investigated. Surprisingly, 2-aryl-substituted systems rearranged regioselectively and in a process whose selectivity proved to be independent of the electronic character of para substituents. The major reaction pathway is suggested to be the one that allows maximum delocalization, and allows it to be maintained for as long as possible. Bridging is invoked to account for the regio- and stereoselectivity. When a nonbridging trimethylsilylmethyl substituent is appended to C2, the regioselectivity is eroded entirely. B3LYP/6-31G(d) calculations corroborate the notion that bridging plays a role. While bridging ought to stabilize an intermediate by allowing delocalization of the charge/spin, there should be an accompanying entropic penalty. To determine the relative importance of enthalpic and entropic factors in determining the product selectivity, the rearrangement of the p-methoxyphenyl-substituted housane was investigated as a function of temperature. Enthalpic factors dominated over the entire temperature range that was explored. Overall, the results indicate that it is possible to influence the direction of migration in housane-derived cation radical rearrangements even when the regiochemical control unit is not directly appended to the migration terminus. This finding suggests that there may be other substituents that can be placed at C2 that could do the same, perhaps more efficiently.     

Multistate reactivity in styrene epoxidation by compound I of cytochrome p450: mechanisms of products and side products formation

Density functional theoretical calculations are used to elucidate the epoxidation mechanism of styrene with a cytochrome P450 model Compound I, and the formation of side products. The reaction features multistate reactivity (MSR) with different spin states (doublet and quartet) and different electromeric situations having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation states. The mechanisms involve state-specific product formation, as follows: a) The low-spin pathways lead to epoxide formation in effectively concerted mechanisms. b) The high-spin pathways have finite barriers for ring-closure and may have a sufficiently long lifetime to undergo rearrangement and lead to side products. c) The high-spin radical intermediate, (4)2(rad)-IV, has a ring closure barrier as small as the C--C rotation barrier. This intermediate will therefore lose stereochemistry and lead to a mixture of cis and trans epoxides. The barriers for the production of aldehyde and suicidal complexes are too high for this intermediate. d) The high-spin radical intermediate, (4)2(rad)-III, has a substantial ring closure barrier and may survive long enough time to lead to suicidal, phenacetaldehyde and 2-hydroxostyrene side products. e) The phenacetaldehyde and 2-hydroxostyrene products both originate from crossover from the (4)2(rad)-III radical intermediate to the cationic state, (4)2(cat,z(2) ). The process involves an N-protonated porphyrin intermediate that re-shuttles the proton back to the substrate to form either phenacetaldehyde or 2-hydroxostyrene products. This resembles the internally mediated NIH-shift observed during benzene hydroxylation.     

Spectral analysis of multichannel MRS data

The use of phased-array receive coils is a well-known technique to improve the image quality in magnetic resonance imaging studies of, e.g., the human brain. It is common to incorporate proton (1H) magnetic resonance spectroscopy (MRS) experiments in these studies to quantify key metabolites in a region of interest. Detecting metabolites in vivo is often difficult, requiring extensive scans to achieve signal-to-noise ratios (SNR) that provide suitable diagnostic results. Combining the MR absorption spectra obtained from several receive coils is one possible approach to increase the SNR. Previous literature does not give a clear overview of the wide range of possible approaches that can be used to combine MRS data from multiple detector coils. In this paper, we consider the multicoil MRS approach and introduce several signal processing tools to address the problem from different nonparametric, semiparametric, and parametric perspectives, depending on the amount of available prior knowledge about the data. We present a numerical study of these tools using both simulated 1H MRS data and experimental MRS data acquired from a 3T MR scanner.     

Fluid dynamics analysis of channel flow geometries for materials characterization in microfluidic devices

The fluid dynamics of geometries for liquid state materials characterization in microfluidic devices are investigated. Numerical simulation together with flow classification criteria are used to explore combinations of geometry and boundary conditions for which the flow type can be adjusted between simple shear and extension, while providing adequate flow strength and a stable environment for material observation. Two classes of flow geometries are identified. Both make use of opposing, laterally offset fluid streams that produce a stagnation point in the center of the geometry. In the first class, the flow type is manipulated by changing parameters inherent to the base geometry. This first case serves as a basis for identifying a second class in which the flow type is manipulated by changing the pressure boundary conditions, while keeping the geometry constant.Electronic Supplementary Material is available for this article if you access the article at .

Ehrhart polynomials and stringy Betti numbers

We study the connection between stringy Betti numbers of Gorenstein toric varieties and the generating functions of the Ehrhart polynomials of certain polyhedral regions. We use this point of view to give counterexamples to Hibi's conjecture on the unimodality of δ-vectors of reflexive polytopes. The first author was partially supported by NSF grant DMS 0500127 and the second author was supported by a Graduate Research Fellowship from the NSF