Copper‐Catalyzed Amidation of Primary and Secondary Alkyl Boronic Esters

The oxidative copper‐catalyzed cross‐coupling of functionalized alkyl boronic esters with primary amides is reported. Through the identification of appropriate diketimine ligands, conditions for efficient coupling of both primary and secondary alkyl boronic esters with diverse primary amides, including acetamide, have been developed.     

Transient spike adding in the presence of equilibria

Many models of neuronal activity exhibit complex oscillations in response to an input from other neurons in a network or to an input from a stimulus. We consider the effect of a single short stimulus on a simple model designed to mimic some features of neuronal dynamics. We focus on the transient response induced by the stimulus, particularly on the spike-adding behaviour of the response. Our main goal is to explain how the transient response is affected by the presence of unstable equilibria. We also investigate the dependence of the number of spikes on the amplitude and duration of the stimulus. In our analysis, we use numerical continuation methods and exploit the presence of different time scales in the model.     

Performance monitoring of a mammalian cell based bioprocess using Raman spectroscopy

Being able to predict the final product yield at all stages in long-running, industrial, mammalian cell culture processes is vital for both operational efficiency, process consistency, and the implementation of quality by design (QbD) practices. Here we used Raman spectroscopy to monitor (in terms of glycoprotein yield prediction) a fed-batch fermentation from start to finish. Raman data were collected from 12 different time points in a Chinese hamster ovary (CHO) based manufacturing process and across 37 separate production runs. The samples comprised of clarified bioprocess broths extracted from the CHO cell based process with varying amounts of fresh and spent cell culture media. Competitive adaptive reweighted sampling (CoAdReS) and ant colony optimization (ACO) variable selection methods were used to enhance the predictive ability of the chemometric models by removing unnecessary spectral information. Using CoAdReS accurate prediction models (relative error of predictions between 2.1% and 3.3%) were built for the final glycoprotein yield at every stage of the bioprocess from small scale up to the final 5000 L bioreactor. This result reinforces our previous studies which indicate that media quality is one of the most significant factors determining the efficiency of industrial CHO-cell processes. This Raman based approach could thus be used to manage production in terms of selecting which small scale batches are progressed to large-scale manufacture, thus improving process efficiency significantly.     

Molecularly Precise Dendrimer–Drug Conjugates with Tunable Drug Release for Cancer Therapy

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer–drug conjugates. Current dendrimer–drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer–drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity.     

An explanation of the unusual strength of the hydrogen bond in small water clusters

We seek to explain why the hydrogen bond possesses unusual strength in small water clusters that account for many of the complex behaviors of water. We have investigated and visualized the donation of covalent character from covalent (sigma) to hydrogen bonds by calculating the eigenvector coupling properties of quantum theory of atoms in molecules (QTAIM), stress tensor σ ( r ), and Ehrenfest Force F ( r ) on the F ( r ) molecular graph. The next-generation three-dimensional (3-D) bond-path framework sets are presented, and only the F ( r ) bond-path framework sets reproduce the earlier finding on the coupling between covalent (sigma) and hydrogen bonds that possess a degree of covalent character. Exploration of the bond-path between the covalent (sigma) and hydrogen bond's critical points provides an explanation for the previously obtained coupling results. The directional character of the covalent (sigma) and hydrogen bonds' 3-D bond-path framework sets for the F ( r ) explains differences found in the earlier results from QTAIM and the stress tensor σ ( r ).     

A mild method for the synthesis of anomerically allylated C-glycopyranosides and C-glycofuranosides

The reaction of glycosyl acetates with allyltrimethylsilane in the presence of zinc bromide has been investigated as a new method for $\text{C}$-glycoside construction.     

Off-shell NN annihilation studied in π+p interactions at 8 and 16 GeV/c

Interactions in which the baryon is emitted forwards in the c.m.s. are studied in 8 and 16 GeV/cπ⁺p collisions. These interactions are interpreted as representing baryon exchange. The properties of such off-shell $\text{N}$N annihilation events are studied. It is found that the multiplicity distribution of the multi-pion system as a function of the effective mass for events with |u_pp| < 1 GeV² is the same as for real $\text{N}\text{N}$ annihilations.     

Zeros ofm-accretive operators in Banach spaces

An operatorT defined on a subsetD(T) of a Banach spaceE and taking values in 2 ^E is said to bem-accretive if for each λ>0, the mappingJ _λ=(I+λT)⁻¹ is a single-valued nonexpansive mapping defined on all ofE. In this paper, facts derived from an elementary analysis of the bahavior of {J _λ x}_λ≧0 for fixedxεD(T) are applied to obtain theorems concerning existence of zeros and surjectivity. Research supported in part by National Science Foundation grant: MCS 76-03945-A01.