The Sodium Borohydride and Sodium Cyanoborohydride Reduction of Unsymmetrically Substituted 3-Chloro-2-propeniminium Salts

A series of 3-substituted-3-chloro-2-propeniminium salts have been reacted with sodium borohydride and/or sodium cyanoborohydride to produce 1-substituted-1-chloro-3-N, N-dimethylamino-1-propenes in good yield.     

Generalizing Kruskal’s theorem to pairs of cohabitating trees

We investigate the extent to which structures consisting of sequences of forests on the same underlying set are well-quasi-ordered under embeddings.     

Development of stable extractive scintillating materials for real-time quantification of radiostrontium in aqueous solutions

Journal of Radioanalytical and Nuclear Chemistry - The research presented here is the development of sensor materials that are applicable for real-time in situ quantification of radiostrontium in...     

trans-(2R,3R)-2,3-Diphenylcyclopropane-1,1-dimethanol: a pivotal diol for the synthesis of novel C2-symmetric ligands for asymmetric transition metal catalysis

Various chiral ligands bearing phosphorus or nitrogen donor atoms were obtained in a straightforward manner starting from trans-(2R,3R)-diphenylcyclopropane-1,1-dimethanol as a key structure. These chiral ligands were tested and compared in palladium(0)-catalyzed asymmetric allylic alkylation reactions (up to 71% ee) and rhodium(I)-catalyzed asymmetric hydrogenations (up to 88% ee). Moreover, in the asymmetric allylic alkylation, we observed excellent activity with a diphosphinite ligand (TOF = 600 mol 17 × [mol Pd × h)^?1].     

Rhodium/olefin-catalyzed reaction of arylboronic acids with an α-acetamido acrylic ester: Mizoroki–Heck-type reaction versus asymmetric conjugate addition

In this paper we present our results concerning the rhodium/olefin-catalyzed reaction of arylboronic acids with an α-acetamido acrylic ester. With a chiral norbornadiene ligand rather low enantioselectivities (up to 21% ee) were obtained. Besides the expected conjugate adduct, we also observed the formation of a significant amount of Mizoroki–Heck-type product. The ratio of the conjugate adduct/Mizoroki–Heck product could be adjusted by a proper choice of the olefin ligand.     

Synthesis and Characterization of Novel Segmented Polyionenes Based on Polydimethylsiloxane Soft Segments

Novel polydimethylsiloxane (PDMS) based polyionenes were synthesized by a modified Menschutkin reaction involving reaction between bromo-terminated PDMS oligomers and various ditertiary amino compounds. In this study, the nature of the hard segment was varied by using various ditertiary amino compounds and in some cases by incorporating chain extenders, while the soft segment content was varied by changing the molecular weight of the PDMS oligomers. The mechanical properties of these materials were found to be dependent on both the nature and amount of the hard segments. These materials also showed distinct evidence of a microphase-separated morphology where under normal conditions, the hard segments formed in what are believed to be cylindrical ion-rich microdomains dispersed randomly in the soft PDMS matrix. When subjected to uniaxial deformation, the ionic cylinders were found to orient along their long axes in the stretch direction.     

Diastereoselectivity is in the Details: Minor Changes Yield Major Improvements to the Synthesis of Bedaquiline**

Bedaquiline is a crucial medicine in the global fight against tuberculosis, yet its high price places it out of reach for many patients. Herein, we describe improvements to the key industrial lithiation-addition sequence that enable a higher yielding and therefore more economical synthesis of bedaquiline. Prioritization of mechanistic understanding and multi-lab reproducibility led to optimized reaction conditions that feature an unusual base-salt pairing and afford a doubling of the yield of racemic bedaquiline. We anticipate that implementation of these improvements on manufacturing scale will be facile, thereby substantially increasing the accessibility of this essential medication.     

Rapid antibody conformational screening by matrix-assisted laser desorption/ionization hydrogen-deuterium exchange mass spectrometry

Recent advances in the field of cancer biology have accelerated the discovery and development of novel biopharmaceuticals. At the forefront of these drug development efforts are high-throughput screening, compressed timelines, and limited sample quantities, all characteristic of the discovery space. To meet program targets, large numbers of protein variants must be produced, screened, and characterized, presenting a daunting analytical challenge. Additionally, the higher-order structure is paramount for protein function and must be monitored as a critical quality attribute. Matrix-assisted laser desorption/ionization mass spectrometry has been utilized as an ultra-fast, automatable, sample-sparing analytical tool for biomolecules. Our group has published applications integrating hydrogen-deuterium exchange mass spectrometry with matrix-assisted laser desorption/ionization mass spectrometry for the rapid conformational characterization of small proteins, the current work expands this application to monoclonal and bi-specific antibodies. This study demonstrates the ability of the methodology, matrix-assisted laser desorption/ionization hydrogen-deuterium exchange mass spectrometry, to detect conformational differences between bi-specific antibodies from different expression hosts. These conformational differences were validated by orthogonal techniques including circular dichroism, nuclear magnetic resonance, and size-exclusion chromatography hydrogen-deuterium exchange mass spectrometry. This work demonstrates the utility of applying the developed methodology as a rapid conformational screening tool to triage samples for further analytical characterization.     

A study of distributed-order time fractional diffusion models with continuous distribution weight functions

The distributed-order time fractional diffusion model with Dirichlet nonhomogeneous boundary conditions on a finite domain is considered. Four choices of continuous distribution weight functions with mean μ and standard deviation σ are investigated to study their impact on both the short-time and long-time solution behavior. An implicit numerical method implemented on a graded mesh is proposed to solve the model and the stability and convergence analysis are presented. Semi-analytic solutions are also derived for these distributions to assess the accuracy of the scheme. Numerical results highlight that the four continuous distribution weight functions produce a short-time solution behavior that is consistent with those solutions from the classical time fractional partial differential equation with fractional order γ* = μ. There are however long-time differences in the solution behavior that become more distinguishable as σ increases. In particular, we find a smaller value of σ produces more diffuse profiles and the diffusion rate slows as σ increases. Furthermore, the asymptotic behavior of the solution may be influenced by the time-fractional orders ranging between the smallest nonzero weight order and mean μ for the continuous uniform and raised cosine distribution weight functions, respectively. Similar findings are also observed for the truncated normal and beta distributions.     

Detection of a P-induced liquid ⇌ solid-phase transformation using multiple acoustic transducers in a multi-anvil apparatus

A technique for detecting and measuring phase transitions in a multi-anvil apparatus by measuring the change in travel time for a longitudinal sound wave as a function of pressure is reported. The system measures the time for pulsed ultrasonic signals to travel through a high pressure assembly with a sample in the center. Upon phase change from liquid to solid, the travel time shows an abrupt decrease due to the intrinsic increase in velocity in the sample and a reduced delay between the triggering of an amplitude threshold and the arrival of the waveform. As a proof of concept, results are shown for mercury as it undergoes pressure-induced liquid ? solid transitions at room temperature. We propose that this non-destructive technique may be valuable in situations where other in situ probing techniques cannot be readily used to provide information about changes of state and potentially to study transition kinetics at high pressures as well.