Enynones in organic synthesis. I. Spiroannulation by tandem oxy-cope rearrangement-electrocyclic ring closure

Bis-acetylenic alcohols of proper design undergo a facile oxy-Cope rearrangement to afford mixtures of E- and Z-enynones. These latter compounds afford methylenecyclopentenones upon enolization and electrocyclic ring closure.     

Symmetrized-lexicographic order and the method of points

A variant of lexicographic order called symmetrized-lexicographic order is defined. The symmetrized-lexicographic order finds its application in the goal programming procedure called the method of points. The symmetrized-lexicographic order is shown to be representable using linear algebra and, thus, the method of points can be implemented as a linear programming problem.     

FAMBE-pH: a fast and accurate method to compute the total solvation free energies of proteins

A fast and accurate method to compute the total solvation free energies of proteins as a function of pH is presented. The method makes use of a combination of approaches, some of which have already appeared in the literature; (i) the Poisson equation is solved with an optimized fast adaptive multigrid boundary element (FAMBE) method; (ii) the electrostatic free energies of the ionizable sites are calculated for their neutral and charged states by using a detailed model of atomic charges; (iii) a set of optimal atomic radii is used to define a precise dielectric surface interface; (iv) a multilevel adaptive tessellation of this dielectric surface interface is achieved by using multisized boundary elements; and (v) 1:1 salt effects are included. The equilibrium proton binding/release is calculated with the Tanford-Schellman integral if the proteins contain more than approximately 20-25 ionizable groups; for a smaller number of ionizable groups, the ionization partition function is calculated directly. The FAMBE method is tested as a function of pH (FAMBE-pH) with three proteins, namely, bovine pancreatic trypsin inhibitor (BPTI), hen egg white lysozyme (HEWL), and bovine pancreatic ribonuclease A (RNaseA). The results are (a) the FAMBE-pH method reproduces the observed pK a's of the ionizable groups of these proteins within an average absolute value of 0.4 p K units and a maximum error of 1.2 p K units and (b) comparison of the calculated total pH-dependent solvation free energy for BPTI, between the exact calculation of the ionization partition function and the Tanford-Schellman integral method, shows agreement within 1.2 kcal/mol. These results indicate that calculation of total solvation free energies with the FAMBE-pH method can provide an accurate prediction of protein conformational stability at a given fixed pH and, if coupled with molecular mechanics or molecular dynamics methods, can also be used for more realistic studies of protein folding, unfolding, and dynamics, as a function of pH.     

Dramatic effects of halogen substitution and solvent on the rates and mechanisms of nucleophilic substitution reactions of aziridines

In a previous study we reported that fluorine substitution at the carbon positions of aziridine results in profound enhancements of the rate of reaction with ammonia, a typical nucleophile, in the gas phase. In this study the investigation is extended to include chloro- and bromoaziridines. Because syntheses are largely performed in the condensed phase, the present computational investigation [(MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level] was conducted with three typical solvents that cover a wide range of polarity: THF, CH3CN, and H2O. Nucleophiles can react with haloaziridines 1 by displacing a substituted amide ion by means of an SN2 mechanism (pathway a), producing 1,2-diaminohaloethanes (from the initially formed dipolar species 2). Alternatively, a rearrangement mechanism involving rate-determining departure of a halide ion (pathway b) to form an imidoyl halide, 3, is possible. Transition-state theory was used to compute relative reaction rates of these mechanistic possibilities and to assess the role of the halogen substituents and the reaction solvent. Gas-phase results provided the basis of mechanistic insights that were more apparent in the absence of intermolecular interactions. Fluoroaziridines were found to react at accelerated rates relative to aziridine exclusively by means of the a Menshutkin-type mechanism (SN2) in each solvent tested, while the reactions of the chloro- and bromoaziridines could be directed toward 2 in the highly nonpolar solvent, cyclohexane, or toward 3 in the more polar solvents. An assessment is made of the feasibility of using this chemistry of the haloazirdines in the synthetic laboratory.     

Template-directed self-assembly of alkanethiol monolayers: selective growth on preexisting monolayer edges

Self-assembled monolayers were investigated for their suitability as two-dimensional scaffolds for the selective growth of alkanethiol edge structures. Heterostructures with chemical contrast could be grown, whose dimensions were governed by both the initial pattern sizes and the process time. n-Octadecanethiol (ODT) was made to expand from the edges of 16-mercaptohexadecanoic acid (MHDA) monolayer patterns. Likewise, 11-mercaptoundecanol (MUD) was grown on MHDA and on ODT monolayer edges. The results of these experiments are in accordance with the moving boundary model for monolayer spreading. In addition to such surface-bound spreading, a vapor-phase contribution to lateral monolayer growth was identified. MUD was observed to be an excellent ink for creating chemical contrast by means of regioselective deposition from a vapor phase. As a proof of principle, ribbons of 11-mercaptoundecanol with submicrometer widths were grown on pentaerythritol-tetrakis(3-mercaptopropionate) edges, and submicrometer wide gold lines were produced by subsequent wet-chemical etching.