Use of β‐cyclodextrins to control the structure of water‐soluble copolymers with hydrophobic parts

In this article, we present the synthesis and characterization of water‐soluble polymers with hydrophobic moieties. The polymers were synthesized in aqueous solutions utilizing β‐cyclodextrins as solubility enhancers to bring the hydrophobic monomers into solution. Polymers were made with different spacing between polymer backbone and phenyl moiety by using styrene, allylbenzene, and 4‐phenyl‐1‐butene as hydrophobic moieties, respectively. The effect of the presence of CDs during synthesis as well as this difference in spacing was investigated by rebinding free β‐CDs to the polymers. The interactions between polymers and CDs were studied by ITC and this revealed some differences between the polymers. Polymers made in the presence of CDs showed a markedly stronger binding to free CDs. The same was observed with polymers with a longer spacing between backbone and phenyl moiety. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6619–6629, 2009     

On the scope of Pd-catalyzed carboamination reactions—synthesis of 2,4-disubstituted pyrrolidines and 2-substituted piperidines and morpholines

The scope of the palladium-catalyzed carboamination reaction for the synthesis of 2-substituted pyrrolidines, piperidines, and morpholines was investigated. Formation of a 2,4-disubstituted pyrrolidine proceeded in high yield but with a diastereoisomeric ratio of only 2:5, favoring the cis-isomer. The diastereoselectivity is hence significantly smaller than that observed previously in the formation of 2,3- and 2,5-disubstituted pyrrolidines. The yields of substituted piperidines and morpholines were lowered by competing Heck arylation reactions. Both the N-substituent and the choice of phosphine ligand for the palladium-catalyzed reaction were determining for the outcome.     

Light-enhanced catalysis by pyridoxal phosphate-dependent aspartate aminotransferase

The mechanisms of pyridoxal 5'-phosphate (PLP)-dependent enzymes require substrates to form covalent "external aldimine" intermediates, which absorb light strongly between 410 and 430 nm. Aspartate aminotransferase (AAT) is a prototypical PLP-dependent enzyme that catalyzes the reversible interconversion of aspartate and α-ketoglutarate with oxalacetate and glutamate. From kinetic isotope effects studies, it is known that deprotonation of the aspartate external aldimine C(α)-H bond to give a carbanionic quinonoid intermediate is partially rate limiting in the thermal AAT reaction. We show that excitation of the 430-nm external aldimine absorption band increases the steady-state catalytic activity of AAT, which is attributed to the photoenhancement of C(α)-H deprotonation on the basis of studies with Schiff bases in solution. Blue light (250 mW) illumination gives an observed 2.3-fold rate enhancement for WT AAT activity, a 530-fold enhancement for the inactive K258A mutant, and a 58600-fold enhancement for the PLP-Asp Schiff base in water. These different levels of enhancement correlate with the intrinsic reactivities of the C(α)-H bond in the different environments, with the less reactive Schiff bases exhibiting greater enhancement. Time-resolved spectroscopy, ranging from femtoseconds to minutes, was used to investigate the nature of the photoactivation of C(α)-H bond cleavage in PLP-amino acid Schiff bases both in water and bound to AAT. Unlike the thermal pathway, the photoactivation pathway involves a triplet state with a C(α)-H pK(a) that is estimated to be between 11 and 19 units lower than the ground state for the PLP-Val Schiff base in water.     

A column generation approach for solving the patient admission scheduling problem

This paper addresses the Patient Admission Scheduling (PAS) problem. The PAS problem entails assigning elective patients to beds, while satisfying a number of hard constraints and as many soft constraints as is possible, and arises at all planning levels for hospital management. There exist a few, different variants of this problem. In this paper we consider one such variant and propose an optimization-based heuristic building on branch-and-bound, column generation, and dynamic constraint aggregation to solve it. We achieve tighter lower bounds than previously reported in the literature and, in addition, we are able to produce new best known solutions for five out of twelve instances from a publicly available repository.     

N‐Butylpyridinium undecachlorocarbadodecaborate and comparison with similar compounds

The title compound, C₉H₁₄N⁺·CHB₁₁Cl₁₁⁻, was obtained in the course of our continuing studies of the low‐melting salts of closo‐ and nido‐carborane cage anions with alkylpyridinium and dialkylimidazolium cations. The title compound is the first example of a pyridinium salt of a perchlorinated carborane anion. The structure consists of one N‐butylpyridinium cation counterbalanced by one perchlorinated carborane cage anion per asymmetric unit. By changing the counter‐ion, different packings are observed, and to try to understand this the new structure is compared with five similar compounds.     

Identification of single stranded regions of DNA by enzymatic digestion with matrix-assisted laser desorption/ionization analysis

Elucidating structure function relationships of DNA in cellular processes requires fast, reliable methods that can be applied to picomole amounts of sample. Higher order structure can be inferred by distinguishing paired and unpaired regions. It is shown here that enzymatic digestion coupled with product analysis by matrix-assisted laser desorption ionization (MALDI) is able to identify unpaired bases within structured DNA regions. The method is demonstrated with DNA duplexes having a five nucleotide mismatch as a 5' overhang, a 3' overhang, and an internal loop. Exo- and endonuclease digestions are performed under solution conditions (temperature, annealing, and enzyme buffers) which promote base pairing and specific enzyme activity. For each type of mismatch, the length and sequence of the single stranded region can be inferred from MALDI spectra taken as a function of digestion time.