The reaction intermediate spectrum. A new type of experiment in tandem mass spectrometry

A new scan is described which responds to ions that are intermediates in the dissociation of a mass-selected parent ion (m_p) to give a mass-selected daughter ion (m_d). The scan gives a simple mass v. abundance output for ions which satisfy this condition. It is implemented here on a BEQQ hybrid mass spectrometer using, in sequence, collision-induced dissociation occurring at high energy in the first reaction region, and low-energy collisional activation in the collision quadrupole. The experiment provides information on reaction sequences not available from single scans of other types. In the several cases examined, it is demonstrated that, among many conceivable fragmentation routes connecting a parent ion with a particular fragment ion, only a few are significant. Examination of reaction intermediate spectra also appears to be a fruitful new approach to mechanistic questions, as illustrated by consideration of the behavior of several isomeric octanones. These new spectra also have analytical value: they show good signal-to-noise ratios and allow ready distinction between isobaric and isomeric ions. A comparison of the reaction intermediate spectrum with a daughter spectrum obtained by the B/E linked-scanning technique reveals the contributions of artifact peaks which result from poor parent ion mass resolution in the latter. Reaction intermediate spectra combine information from the daughter spectra of m_p and the parent spectra of m_d and, as a specified portion of this data domain, have unique characteristics.     

Ring-Opening Polymerization of γ-(4-Vinylbenzyl)-(L)-Glutamate N-Carboxyanhydride for the Synthesis of Functional Polypeptides

Introducing various pendant functional groups and building blocks of interest to polypeptides in a highly efficient, controlled manner is crucial to access polypeptide materials with desired structures and functions. In this study, we synthesized γ-(4-vinylbenzyl)-(L)-glutamate N-carboxyanhydride (VB-Glu-NCA), which was readily obtained and purified in large quantity. VB-Glu-NCA monomer was subsequently used for the synthesis of polypeptides containing conjugation-amenable, pendant vinyl functional groups. Controlled, living polymerizations of VB-Glu-NCA were achieved by using hexamethyldisilazane (HMDS) as the initiator, catalytic amounts of 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as the co-catalyst, and nitrobenzene as the inhibitor of radical-induced side reactions on the vinyl group of VB-Glu-NCA. The resulting poly(γ-(4-vinylbenzyl)-(L)-glutamate) (PVBLG) gave rise to polypeptides containing pendant functional groups or moieties through various vinyl chemistries.     

Practical and highly selective oxazolidinethione-based asymmetric acetate aldol reactions with aliphatic aldehydes

[reaction: see text] The utility of a valine-derived oxazolidinethione for auxiliary-based asymmetric acetate aldol reactions is reported. Titanium(IV) chloride, along with (-)-sparteine and N-methylpyrrolidinone, is employed for enolization. Subsequent aldol reaction with aliphatic aldehydes occurs with high diastereoselectivity (from 92:8 to 99:1 dr).     

Solvothermal depolymerization and recrystallization of imine-linked two-dimensional covalent organic frameworks

Mechanistic understanding into the formation and growth of imine-linked two-dimensional (2D) covalent organic frameworks (COFs) is needed to improve their materials quality and access larger crystallite sizes, both of which limit the promise of 2D COFs and 2D polymerization techniques. Here we report a previously unknown temperature-dependent depolymerization of colloidal 2D imine-linked COFs, which offers a new means to improve their crystallinity. 2D COF colloids form at room temperature but then depolymerize when their reaction mixtures are heated to 90 °C. As the solutions are cooled back to room temperature, the 2D COFs repolymerize and crystallize with improved crystallinity and porosity, as characterized by X-ray diffraction, infrared spectroscopy and N₂ porosimetry. The evolution of COF crystallinity during the solvothermal depolymerization and repolymerization processes was characterized by in situ wide angle X-ray scattering, and the concentrations of free COF monomers as a function of temperature were quantified by variable temperature ¹H NMR spectroscopy. The ability of a 2D COF to depolymerize under these conditions depends on both the identity of the COF and its initial materials quality. For one network formed at room temperature (TAPB-PDA COF), a first depolymerization process is nearly complete, and the repolymerization yields materials with dramatically enhanced crystallinity and surface area. Already recrystallized materials partially depolymerize upon heating their reaction mixtures a second time. A related 2D COF (TAPB-DMTA COF) forms initially with improved crystallinity compared to TAPB-PDA COF and then partially depolymerizes upon heating. These results suggest that both high materials quality and network-dependent properties, such as interlayer interaction strength, influence the extent to which 2D COFs resist depolymerization. These findings offer a new means to recrystallize or solvent anneal 2D COFs and may ultimately inform crystallization conditions for obtaining large-area imine-linked two-dimensional polymers from solution.

Conditions for which imine-linked 2D COF polymerizations are temperature-sensitive are identified that enable a dissolution/repolymerization process akin to molecular recrystallization.     

Chemistry of constrained dioxocyclam ligands with Co(III): unusual examples of C-H and C-N bond cleavage

The reactions between H(2)dc3 and Co(acac)(3) have been studied in the presence and absence of base. In the presence of base, a complex with an intramolecular Co-C bond, Co(dc3-C-(8))(H(2)O), 1, is formed, presumably through heterolytic C-H bond activation. An X-ray crystallographic study demonstrates the presence of a Co-C bond and shows that the diazacyclooctane (daco) subunit adopts the chair-boat conformation with respect to the metal. The cobalt-carbon bond induces strain in the macrocycle as demonstrated by bond angles significantly deviating from tetrahedral. The (13)C NMR resonance of the carbon atom bound to cobalt (-10.5 ppm) suggests significant ionic character in the cobalt-carbon bond. However, we were unable to cleave this bond in the presence of strong acid. In the absence of base, the reaction of Co(acac)(3) with H(2)dc3 resulted in C-N cleavage of the ligand and the formation of a complex of dioxocyclam, Co(dc)(acac), 2. This complex has subsequently been prepared in high yield by the reaction of Co(acac)(3) with dioxocyclam. An X-ray crystallographic study demonstrates that dioxocyclam adopts the heretofore unreported cis configuration, having folded along a N-Co-N axis that is perpendicular to the Co-acac plane.     

Synthesis of a cyclic peptide containing norlanthionine: effect of the thioether bridge on peptide conformation

Two diastereomeric analogues of ring C of nisin incorporating a novel norlanthionine residue have been synthesized via a triply orthogonal protecting group strategy. A full structural study was carried out by NMR, which elucidated the conformational properties of the two peptides and enabled the identity of each diastereoisomer to be proposed.     

A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions

A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 °C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells.