Odonnellbuch1068

Synthetic peptides represent an important and expanding class of therapeutics. Despite having a relatively small size as compared to monoclonal antibodies and other proteins, synthetic peptides are subject to many complex structural modifications originating from the starting materials, manufacturing process, and storage conditions. Although mass spectrometry has been increasingly used to characterize impurities of synthetic peptides, systematic review of this field is scarce. In this paper, an overview of the impurities in synthetic peptide therapeutics is provided in the context of how the knowledge from detailed characterization of the impurities using liquid chromatography-mass spectrometry (LC-MS) can be used to develop the manufacturing process and control strategy for synthetic peptide therapeutics following the critical quality attribute (CQA)-driven and risk-based approach. The thresholds for identifying and controlling the impurities are discussed based on currently available regulatory guidance. Specific LC-MS techniques for identification of various types of impurities based on their structural characteristics are discussed with the focus on structural isomers and stereoisomers (i.e., peptide epimers). Absolute and relative quantitation methods for the peptide impurities are critiqued. Potential pitfalls in characterization of synthetic peptide therapeutics using LC-MS are discussed. p38 MAPK inhibitor review Finally, a systematic LC-MS workflow for characterizing the impurities in synthetic peptide therapeutics is proposed, and future perspectives on applying emerging LC-MS techniques to address the remaining challenges in the development of synthetic peptide therapeutics are presented.A barrier to the widespread adoption of electric vehicles is enabling fast charging lithium-ion batteries. At normal charging rates, lithium ions intercalate into the graphite electrode. At high charging rates, lithiation is inhomogeneous, and metallic lithium can plate on the graphite particles, reducing capacity and causing safety concerns. We have built a cell for conducting high-resolution in situ X-ray microtomography experiments to quantify three-dimensional lithiation inhomogeneity and lithium plating. Our studies reveal an unexpected correlation between these two phenomena. During fast charging, a layer of mossy lithium metal plates at the graphite electrode-separator interface. The transport bottlenecks resulting from this layer lead to underlithiated graphite particles well-removed from the separator, near the current collector. These underlithiated particles lie directly underneath the mossy lithium, suggesting that lithium plating inhibits further lithiation of the underlying electrode.A handful of oxygen-activating enzymes has recently been found to contain Fe/Mn active sites, like Class 1c ribonucleotide reductases and R2-like ligand-binding oxidase, which are closely related to their better characterized diiron cousins. These enzymes are proposed to form high-valent intermediates with Fe-O-Mn cores. Herein, we report the first examples of synthetic Fe/Mn complexes that mimic doubly bridged intermediates proposed for enzymatic oxygen activation. Fe K-edge extended X-ray absorption fine structure (EXAFS) analysis has been used to characterize the structures of each of these compounds. Linear compounds accurately model the Fe···Mn distances found in Fe/Mn proteins in their resting states, and doubly bridged diamond core compounds accurately model the distances found in high-valent biological intermediates. Unlike their diiron analogues, the paramagnetic nature of Fe/Mn compounds can be analyzed by EPR, revealing S = 1/2 signals that reflect antiferromagnetic coupling between the high-spin Fe(III) and Mn(III) units of heterobimetallic centers. These compounds undergo electron transfer with various ferrocenes, linear compounds being capable of oxidizing diacetyl ferrocene, a weak reductant, and diamond core compounds being capable of oxidizing acetyl ferrocene. Diamond core compounds can also perform HAT reactions from substrates with X-H bonds with bond dissociation free energies (BDFEs) up to 75 kcal/mol and are capable of oxidizing TEMPO-H at rates of 0.32-0.37 M-1 s-1, which are comparable to those reported for some mononuclear FeIII-OH and MnIII-OH compounds. However, such reactivity is not observed for the corresponding diiron compounds, a difference that Nature may have taken advantage of in evolving enzymes with heterobimetallic active sites.Aqueous zinc-ion batteries (ZIBs) have attracted considerable attention because of their low cost, high intrinsic safety, and high volumetric capacity. However, unexpected dendrite growth and side reactions that arise at the Zn anode can severely hinder the mass adoption of ZIBs in practical applications. Herein, we report a dendrite-free ZIB anode via the hybridization of a eutectic ZnAl alloy with a copper mesh (denoted as ZnAl@Cu-mesh). The eutectic structure of the ZnAl alloy is composed of alternating Zn blocks and Al nanoflakes. The Al nanoflakes sacrificially consume the oxygen in the electrolyte to form an Al2O3/Al shell-core structure, which in turn guides the Zn deposition process by restraining the lateral diffusion of zinc ions and hence reducing the extent of dendrite formation. This process can synergistically reduce the likelihood of Zn passivation, which allows the Zn region to remain electrochemically active for the Zn stripping/plating process. Meanwhile, a copper mesh is used as a scaffold to provide uniform electric field distribution. As a result, the symmetric ZnAl@Cu-mesh//ZnAl@Cu-mesh cell presents appreciably low polarization (30 mV at 0.5 mA cm-2) and excellent cycling stability (240 h at 0.5 mA cm-2), as compared to Zn//Zn. Based on the postmortem investigation, ZnAl@Cu-mesh is able to retain a dendrite-free morphology after cycling at 1 mA cm-2, while significant dendrite formation can be observed for Zn. More impressively, the ZnAl@Cu-mesh//V2O5 full cell is able to achieve a 95% capacity retention after 2000 cycles at 2 A g-1, whereas its counterpart assembled with Zn fails after only 750 cycles because of short-circuit. Thus, the composite alloying strategy proposed in this work may provide an appealing direction toward the future development of dendrite-free anodes for rechargeable secondary batteries.