Vibrational lifetimes of molecular adsorbates on metal surfaces

We report density functional theory calculations of electron-hole pair induced vibrational lifetimes of diatomic molecules adsorbed on metal surfaces. For CO on Cu(100), Ni(100), Ni(111), Pt(100), and Pt(111), we find that the C-O internal stretch and the bending modes have lifetimes in the 1-6 ps range, and that the CO-surface stretch and the frustrated translational modes relax more slowly, with lifetimes >10 ps for all cases except CO on Ni(111). This strong mode selectivity confirms earlier calculations for CO on Cu(100) and demonstrates that the trends carry over to other metal substrates. In contrast, for NO adsorbed on Pt(111), whereas we still find that the bending mode has the shortest lifetime, about 1.3 ps, we predict the other three modes to have almost equal lifetimes of 8-10 ps. Similarly, for CN adsorbed on Pt(111), we calculate that the internal stretching and molecule-surface stretching modes have approximately equal lifetimes of about 15 ps. Our results are in reasonable agreement with experiment, where available. We discuss some of the underlying factors that may contribute to the observed mode selectivity with adsorbed CO and the altered selectivity with NO and CN.     

A chondroitin sulfate small molecule that stimulates neuronal growth

Chondroitin sulfate glycosaminoglycans are sulfated polysaccharides involved in cell division, neuronal development, and spinal cord injury. Here, we report the synthesis and identification of a chondroitin sulfate tetrasaccharide that stimulates the growth and differentiation of neurons. These studies represent the first, direct investigations into the structure-activity relationships of chondroitin sulfate using homogeneous synthetic molecules and define a tetrasaccharide as a minimal motif required for activity.     

Improving Physical Properties via C?H Oxidation: Chemical and Enzymatic Approaches

Physicochemical properties constitute a key factor for the success of a drug candidate. Whereas many strategies to improve the physicochemical properties of small heterocycle‐type leads exist, complex hydrocarbon skeletons are more challenging to derivatize because of the absence of functional groups. A variety of C H oxidation methods have been explored on the betulin skeleton to improve the solubility of this very bioactive, yet poorly water‐soluble, natural product. Capitalizing on the innate reactivity of the molecule, as well as the few molecular handles present on the core, allowed oxidations at different positions across the pentacyclic structure. Enzymatic oxidations afforded several orthogonal oxidations to chemical methods. Solubility measurements showed an enhancement for many of the synthesized compounds.     

The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12) expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

Background  

Stromal cell-derived factor 1 (SDF-1 or CXCL12) is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI) injury in neonatal brain.     

Transition state barriers in multidimensional Marcus theory

Multidimensional Marcus theory is the extension of traditional Marcus theory to systems in which multiple particles are transferred. Rather than the intersecting parabolas of Marcus theory, multidimensional Marcus theory involves the intersection of paraboloids. In this paper, we examine the conditions under which a full multidimensional treatment of these paraboloids is necessary and when it is possible to use a simpler one-dimensional formalism. In particular, we examine transition state barrier energies, which are essential parameters in many reaction rate equations, and which depend on the formalism used. We find, based on both analytic calculations and numerical simulation, that the reduced one-dimensional treatment yields excellent agreement with the exact, multidimensional results over a wide variety of conditions for one particular choice of the single collective reaction coordinate. We also outline a procedure for calculating accurate multidimensional transition state barrier energies and apply it to a two-dimensional model of proton-coupled electron transfer.     

Synthesis of 4-alkyl-, 4-aryl- and 4-arylamino-5-aminoisoquinolin-1-ones and identification of a new PARP-2 selective inhibitor

The considerable interest in substituted isoquinolin-1-ones related to 5-aminoisoquinolin-1-one (5-AIQ) as drugs points to a need for an efficient and straightforward synthesis of the 4,5-disubstituted bicycles. Bromination of 5-nitroisoquinolin-1-one gave 4-bromo-5-nitroisoquinolin-1-one but neither this nor 5-amino-4-bromoisoquinolin-1-one would participate in Pd-catalysed couplings. Protection of the lactam as 1-methoxy- and 1-benzyloxy-4-bromo-5-nitroisoquinolines, however, permitted Stille, Suzuki and Buchwald-Hartwig couplings to take place in high yields, insensitive to electronic demands and severe steric bulk in the arylboronic acids. Lithiation of 4-bromo-1-methoxy-5-nitroisoquinoline and quench with iodomethane gave 1-methoxy-4-methyl-5-nitroisoquinoline in low yield. Demethylation of the 1-methoxy-4-substituted-5-nitroisoquinolines with hydrogen bromide gave 4-substituted-5-nitroisoquinolin-1-ones, whereas hydrogenolytic debenzylation was achieved with simultaneous reduction of the 5-nitro group. 5-Amino-4-(4-trifluoromethylphenyl)isoquinolin-1-one was identified as a new potent and selective inhibitor of poly(ADP-ribose)polymerase-2 (PARP-2).