ChemInform Abstract: The Formation and Characterization of Three-Membered Ring Carbanions in the Gas Phase: An Experimental and Theoretical Investigation of the Conjugate Bases of Thiirane, Thiirane S-Oxide, and Thiirane S,S-Dioxide.

Abinitio molecular orbital calculations are reported for several cyclic and acyclic sulfones. The geometries of XSO2Y, where X, Y = H, F, or CH3 are optimized at the STO-3G* level. Similar calculations are reported for the smallest cyclic sulfone, thiirane-1,1 -dioxide, as well as the corresponding sulfoxide, thiirane-1-oxide, and the parent sulfide, thiirane. Where comparison with experiment is possible, the agreement is satisfactory. In order to consider the possibility of substantial differences between axial and equatorial S—O bonds in the gas phase, as observed in the crystal structure of 5H,8H-dibenzo[d,f][1,2]-dithiocin-1,1-dioxide, STO-3G* calculations are reported for a six-membered ring, thiane-1,1-dioxide, and a model eight-membered ring. Limited geometry optimization of the axial and equatorial S—O bonds in the chair conformations of the six- and eight-membered rings leads to bond lengths of 1.46 Å with the difference being less than 0.01 Å.

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Experimental and theoretical investigation of gas phase complexes between chloride ion and some chloroethenes

International Journal of Mass Spectrometry ◽

10.1016/s1387-3806(98)14130-1 ◽

1998 ◽

Vol 179-180 ◽

pp. 349-357 ◽

Cited By ~ 4

Author(s):

Alessandro Bagno ◽

Anna Donò ◽

Silvia Martinucci ◽

Cristina Paradisi ◽

Gianfranco Scorrano

Keyword(s):

Gas Phase ◽

Theoretical Investigation ◽

Chloride Ion

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The gas phase characterization of perfluorobutyryl chloride, C3F7COCl, using chirped pulse Fourier transform microwave spectroscopy

Chemical Physics Letters ◽

10.1016/j.cplett.2009.10.043 ◽

2009 ◽

Vol 483 (1-3) ◽

pp. 21-24 ◽

Cited By ~ 6

Author(s):

G.S. Grubbs ◽

S.A. Cooke

Keyword(s):

Fourier Transform ◽

Gas Phase ◽

Microwave Spectroscopy ◽

Chirped Pulse ◽

Fourier Transform Microwave Spectroscopy ◽

Phase Characterization

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ChemInform Abstract: Characterization of Ionized Carbenes in the Gas Phase

ChemInform ◽

10.1002/chin.200112300 ◽

2001 ◽

Vol 32 (12) ◽

pp. no-no

Author(s):

Robert Flammang ◽

Minh Tho Nguyen ◽

Guy Bouchoux ◽

Pascal Gerbaux

Keyword(s):

Gas Phase ◽

Abstract Characterization

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State-of-the-Art Native Mass Spectrometry and Ion Mobility Methods to Monitor Homogeneous Site-Specific Antibody-Drug Conjugates Synthesis

Pharmaceuticals ◽

10.3390/ph14060498 ◽

2021 ◽

Vol 14 (6) ◽

pp. 498

Author(s):

Evolène Deslignière ◽

Anthony Ehkirch ◽

Bastiaan L. Duivelshof ◽

Hanna Toftevall ◽

Jonathan Sjögren ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Phase ◽

Ion Mobility ◽

State Of The Art ◽

Native Mass Spectrometry ◽

Site Specific ◽

Drug Conjugates ◽

Conjugation Process ◽

Antibody Drug

Antibody-drug conjugates (ADCs) are biotherapeutics consisting of a tumor-targeting monoclonal antibody (mAb) linked covalently to a cytotoxic drug. Early generation ADCs were predominantly obtained through non-selective conjugation methods based on lysine and cysteine residues, resulting in heterogeneous populations with varying drug-to-antibody ratios (DAR). Site-specific conjugation is one of the current challenges in ADC development, allowing for controlled conjugation and production of homogeneous ADCs. We report here the characterization of a site-specific DAR2 ADC generated with the GlyCLICK three-step process, which involves glycan-based enzymatic remodeling and click chemistry, using state-of-the-art native mass spectrometry (nMS) methods. The conjugation process was monitored with size exclusion chromatography coupled to nMS (SEC-nMS), which offered a straightforward identification and quantification of all reaction products, providing a direct snapshot of the ADC homogeneity. Benefits of SEC-nMS were further demonstrated for forced degradation studies, for which fragments generated upon thermal stress were clearly identified, with no deconjugation of the drug linker observed for the T-GlyGLICK-DM1 ADC. Lastly, innovative ion mobility-based collision-induced unfolding (CIU) approaches were used to assess the gas-phase behavior of compounds along the conjugation process, highlighting an increased resistance of the mAb against gas-phase unfolding upon drug conjugation. Altogether, these state-of-the-art nMS methods represent innovative approaches to investigate drug loading and distribution of last generation ADCs, their evolution during the bioconjugation process and their impact on gas-phase stabilities. We envision nMS and CIU methods to improve the conformational characterization of next generation-empowered mAb-derived products such as engineered nanobodies, bispecific ADCs or immunocytokines.

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