Structure and fragmentation mechanisms of organic ions in the mass spectrometer

Cooks, R. Graham; Howe, Ian; Williams, Dudley H.

doi:10.1002/oms.1210020202

Cited by 137 publications

(21 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since it is observed here, higher activation energies are suggested to be associated with radical losses rather than with the competitive elimination reactions, the lower frequency factors for elimination reactions counterbalancing the energetic terms and leading to comparable fragmentation rates. 22 This points to the iimited validity of the even electron ion + even electron ion nile.' Additional examples of competitive radical and neutral losses on collision induced dissociation of protonated species are a~ailable.~,*~ From these results it is concluded that small proto-nated ions follow characteristic fragmentation patterns just as do odd electron ions.…”

Section: Discussionmentioning

confidence: 98%

Fragmentation of even electron ions. Protonated ketones and ethers

Sigsby

Day

Cooks

1979

Org. Mass Spectrom.

View full text Add to dashboard Cite

A systematic study of the types of fragmentation undergone by intemdly excited protonated molecules is presented. Two representative functional groups, ethers and ketones, are selected, and both aliphatic and aromatic substituents are examined. The ions are formed by protonation or alkylation in a chemical ionization source, and caused to fragment by collision at high relative kinetic energy. The prevalence of 1,3-reaurangements and the breakdown of the even eleetron fragmentation rule highlight the ion chemistry uncovered here. Specific findings include: (i) electron unpairing reactions associated with -1 radical loss are common. These are probably energetically less favorable simple bond cleavages and are observed in competition with entropically less favorable elimination reactions. (ii) Alkane elimination is a characteristic reaction, which often occurs by a four-centered mechanism. Several variations on this reaction type are encountered. (%) AlLene elimination is another ubiquitous reaction which occurs by a four-centered mechanism in the systems studied here. Competition between atkene and alkane loss is extremely sensitive to the particular system in hand.

show abstract

Section: Discussionmentioning

confidence: 98%

Fragmentation of even electron ions. Protonated ketones and ethers

Sigsby

Day

Cooks

1979

Org. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…The most notable phenomenon in our study is that the Cl-KIEs of DCM changed from large normal Cl-KIEs to extremely large inverse Cl-KIEs as the CEs varied from 0 to 60 eV, which has never been reported previously and is challenging to explain. To interpret this phenomenon, we refer to the theory in terms of competitive dechlorination reactions in EI-MS [34,35]. We take the reactions of CH2 35 Cl 37 Cl •+ →CH2 35 Cl + (H) and CH2 35 Cl 37 Cl •+ →CH2 37 Cl + (L) of DCM for example, which can be regarded as two isotope-competitive reactions during CID in MS/MS.…”

Section: Isotope-competitive Dechlorination Reactionsmentioning

confidence: 99%

Energy‐dependent normal and unusually large inverse chlorine kinetic isotope effects of simple chlorohydrocarbons in collision‐induced dissociation by gas chromatography‐electron ionization‐tandem mass spectrometry

et al. 2020

View full text Add to dashboard Cite

Kinetic isotope effects (KIEs) taking place in mass spectrometry (MS) can provide indepth insights into the fragmental behaviors of compounds in MS. Yet the mechanisms of KIEs in collision-induced dissociation (CID) in tandem MS are unclear, and information about chlorine KIEs (Cl-KIEs) of organochlorines in MS is particularly scarce. This study investigated the Cl-KIEs of dichloromethane, trichloroethylene and tetrachloroethylene during CID using gas chromatography-electron ionization triplequadrupole tandem MS. Cl-KIEs were measured with MS signal intensities, and their validity was confirmed in terms of chromatograms, crosstalk effects and background subtraction influences. All the organochlorines presented large inverse Cl-KIEs, showing the largest values of 0.492, 0.910 and 0.892 at the highest collision energy for dichloromethane, trichloroethylene and tetrachloroethylene, respectively. For dichloromethane, both intra-ion and inter-ion Cl-KIEs were studied, within the ranges of 0.492-1.020 and 0.614-1.026, respectively, showing both normal and inverse Cl-KIEs depending on collision energies. The observed Cl-KIEs generally declined with the increasing collision energies from 0-60 eV, but were inferred to be independent of MS signal intensities. The normal Cl-KIEs were explained with the quasi-equilibrium theory and zero point energy theory, and the inverse Cl-KIEs were interpreted with isotope-competitive reactions relevant to transition state theory. The Cl-KIEs are dominated by critical energies at low internal energies, while controlled by rotational barriers (or looseness/tightness of transition states) at high internal energies. It is concluded that the Cl-KIEs may depend on critical energies, bond strengths, available internal energies, and transition state looseness/tightness. The findings of this study yield new insights into the fundamentals of Cl-KIEs of organochlorines during CID, Page 3 and may be conducive to elucidating the mechanisms of KIEs in collision-induced and photo-induced reactions in the actual world.

show abstract

“…For example, MS/MS experiments on "chiral" complexes that measure the specific dissociation energies with the "kinetic method" [88] was previously discussed by Djerassi and coworkers [89]. In these communications from the 1960s, a thorough understanding of electron ionization mass spectra allowed one to resolve structural and stereochemical problems for steroidal molecules [90]. The relative lack of 3D structural information from MS spectra is compensated when highly automated lC-uV-MS/MS-NMR platforms are utilized, as has been shown in several examples [91][92][93][94].…”

Section: The Role Of Ms In the Elucidation Of Chemical Structuresmentioning

confidence: 99%

MS Applications in Support of Medicinal Chemistry Sciences

Honing¹,

Ingelse²,

Pramanik³

2013

Mass Spectrometry for Drug Discovery and Drug Development

View full text Add to dashboard Cite

In the drug discovery process, medicinal chemistry plays a crucial role in the optimal design and synthesis (production) of new chemical entities (NCEs) or new biological entities (NBEs); this is true for a single entity as well as a complete compound library. A key requirement in this field of science is the optimization of both the chemical and the biological properties of these potential drug-like compounds. Important criteria are the design of efficient synthesis routes, the balancing of the physical chemical properties with optimal in vitro and in vivo drug metabolism and pharmacokinetic (DMPK) processes, and a profound understanding of the pharmacodynamics in the appropriate pharmacological models. In the lead optimization stage, an important step is scaling up the synthesis route as needed for the execution of toxicology studies and the screening of suitable drug formulations. In summary, medicinal chemistry support includes participating in a large variety of activities and decision making processes that play a key role in the search for either a "first in class" new drug or a "best in class" new drug [1].These "drug discovery" processes are continuously under pressure, as the research and development (R&D) costs continue to increase and more data are requested before new drug candidates are taken into (pre-)clinical development. Hence, the choice of "targeted" high-throughput screening (HTS) libraries, the process of hit appraisal, and the understanding of target-ligand interactions can be considered the starting points for a new drug discovery program [2]. Next, the main focus is on the discovery of a lead compound; typically, this is a compound showing promising data regarding target affinity, reasonable efficacy in cellular models, good physical chemical parameters (i.e., a "drug-like" compound), and acceptable oral bioavailability in Mass Spectrometry for Drug Discovery and Drug Development, First Edition. Edited by Walter A. Korfmacher.

show abstract

Structure and fragmentation mechanisms of organic ions in the mass spectrometer

Cited by 137 publications

References 86 publications

Fragmentation of even electron ions. Protonated ketones and ethers

Fragmentation of even electron ions. Protonated ketones and ethers

Energy‐dependent normal and unusually large inverse chlorine kinetic isotope effects of simple chlorohydrocarbons in collision‐induced dissociation by gas chromatography‐electron ionization‐tandem mass spectrometry

MS Applications in Support of Medicinal Chemistry Sciences

Contact Info

Product

Resources

About