Electrophilic additions to allenes. VII. The role of steric versus electronic effects in the reactions of areneselenenyl halides with allenes

The reactions of benzeneselenenyl chloride, bromide, and 2,4,6-trimethylbenzeneselenenyl bromide with alkyl 1,3-disubstituted allenes in methylene chloride solution have been investigated. While kinetic data are in accord with similar rate determining transition states, exhibiting strong steric effects for ail three species, the product distributions show changes in both chemoselectivity and configurational-selectivity in accord with two different types of steric interaction mechanisms during the product determining transition states. A mechanism involving rate limiting formation of alkylideneseleniranium ions and/or alkylideneepiselenuranes, followed by isomerization between the alkylideneseleniranium ions by a path not involving allylic ions, prior to the product determining transition states, is proposed.

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Electrophilic additions to allenes. VI. The role of steric versus electronic effects in the reactions of arenesulphenyl halides with allenes

Canadian Journal of Chemistry ◽

10.1139/v80-438 ◽

1980 ◽

Vol 58 (24) ◽

pp. 2737-2744 ◽

Cited By ~ 4

Author(s):

Dennis G. Garrattz ◽

Pierre L. Beaulieu

Keyword(s):

Positive Charge ◽

Steric Effects ◽

Rate Data ◽

Electronic Effects ◽

Rate Determining Step ◽

Minimal Importance ◽

Electrophilic Additions

The role of steric and electronic effects during the rate and product determining steps for the addition of arenesulphenyl chlorides to 1,3-disubstituted allenes has been briefly examined. Both effects appear to be generally of minimal importance during the rate determining step. The available rate data indicate the presence of little, if any, build up of positive charge on sulphur. These results are interpreted in terms of an SN2 attack on bivalent sulphur leading to an alkylidenethiiranium ion intermediate. Steric effects are of greater importance in the product determining step, particularly when the sulphenyl chlorides possess two bulky ortho substituents, as in the case of 2,4,6-triisopropylbenzenesulphenyl chloride.

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Addition of arenesulphenyl chlorides to 2-methylenebicyclo[2.2.1]hept-5-ene: effect of increasing electron demand upon the rate and product determining transition states

Canadian Journal of Chemistry ◽

10.1139/v80-160 ◽

1980 ◽

Vol 58 (10) ◽

pp. 1021-1029 ◽

Cited By ~ 4

Author(s):

Dennis G. Garratt ◽

Pierre L. Beaulieu ◽

Veronique M. Morisset

Keyword(s):

Double Bond ◽

Chloride Solution ◽

Methylene Chloride ◽

Transition States ◽

Exocyclic Double Bond ◽

Electrophilic Attack ◽

Methylene Chloride Solution ◽

Major Species ◽

Electron Demand

The rates and products of addition of a series of sixteen arenesulphenyl chlorides to 2-methylenebicyclo[2.2.1]hept-5-ene, 7, and the E, Z isomeric 2-ethylidenebicyclo[2.2.1]hept-5-enes, 8 and 9, have been determined in methylene chloride solution. The major species from attack on 7 is always endo-3-arylthio-1-chloromethyltricyclo[2.2.1.02,6]heptane, the product of exo attack upon the endocyclic double bond with homoallylic participation of the exocyclic π system. No evidence was found for initial electrophilic attack upon the exocyclic double bond.

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The steric course of some electrophilic additions to the tetrahydropyridazine ring moiety of benzo[g]pyridazino[1,2-b]-phthalazine-6, 13-dione derivatives. II.

Canadian Journal of Chemistry ◽

10.1139/v97-040 ◽

1997 ◽

Vol 75 (3) ◽

pp. 348-355 ◽

Cited By ~ 5

Author(s):

María Del Carmen Cano ◽

Fernando Gómez-Contreras ◽

Ana María Sanz ◽

María Josefa Rodriguez Yunta

Keyword(s):

Double Bond ◽

Alder Reaction ◽

Diels Alder ◽

Reaction Products ◽

Electronic Effects ◽

Electrophilic Attack ◽

Diels Alder Reaction ◽

Pyridazine Ring ◽

Product Distributions ◽

Electrophilic Additions

The stereochemical features involved in electrophilic additions to the ring A moiety in diazatetracyclic analogues of anthracyclinones have been investigated. The 1-methyl and 1,3-dimethyl derivatives 2a and 2b were selected as the substrates and made to react with bromine azide, iodine azide, and NBS–EtOH in order to evaluate the influence of the C-1 substituent on the product distributions. Electrophilic attack at the C-2/C-3 double bond occurs mainly in the less hindered anti fashion. The nucleophilic step governs the stereochemistry of the reaction products. Conformational factors are predominant over the steric and electronic effects originated by the ring A substituents, since axial antiparallel attack of the nucleophile on the intermediate epihalonium ion is clearly preferred to the equatorial approach. Keywords: diazatetracycles, Diels–Alder reaction, electrophilic addition, anthracyclinone analogues, pyridazine ring.

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Protective Role of Glutathione in the Hippocampus after Brain Ischemia

International Journal of Molecular Sciences ◽

10.3390/ijms22157765 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7765

Author(s):

Youichirou Higashi ◽

Takaaki Aratake ◽

Takahiro Shimizu ◽

Shogo Shimizu ◽

Motoaki Saito

Keyword(s):

Oxidative Stress ◽

Neuronal Death ◽

Excitatory Amino Acid ◽

Ischemia Reperfusion ◽

Thiol Group ◽

Protective Role ◽

Key Factor ◽

Rate Limiting ◽

Cysteine Uptake

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

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ChemInform Abstract: An ab initio SCF/CI Study on the Role of C2v Transition States in Thermal and Photochemical Sigmatropic Shifts (

Chemischer Informationsdienst ◽

10.1002/chin.198625132 ◽

1986 ◽

Vol 17 (25) ◽

Author(s):

G. J. M. DORMANS ◽

H. M. BUCK

Keyword(s):

Ab Initio ◽

Transition States

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Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽

10.3390/cancers13040909 ◽

2021 ◽

Vol 13 (4) ◽

pp. 909

Author(s):

Krzysztof Kotowski ◽

Jakub Rosik ◽

Filip Machaj ◽

Stanisław Supplitt ◽

Daniel Wiczew ◽

...

Keyword(s):

Current Knowledge ◽

Treatment Options ◽

Protein Structures ◽

New Drugs ◽

Proliferating Cells ◽

Cancer Tissues ◽

The Impact ◽

Rate Limiting ◽

Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

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Fast Kinetics Reveals Rate-Limiting Oxidation and the Role of the Aromatic Cage in the Mechanism of the Nicotine-Degrading Enzyme NicA2

Biochemistry ◽

10.1021/acs.biochem.0c00855 ◽

2021 ◽

Vol 60 (4) ◽

pp. 259-273

Author(s):

Margarita A. Tararina ◽

Katie K. Dam ◽

Manaswni Dhingra ◽

Kim D. Janda ◽

Bruce A. Palfey ◽

...

Keyword(s):

Fast Kinetics ◽

Degrading Enzyme ◽

Aromatic Cage ◽

Rate Limiting

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The addition of 2,4-dinitrobenzenesulphenyl chloride to 1,3-disubstituted allenes: a reexamination

Canadian Journal of Chemistry ◽

10.1139/v79-019 ◽

1979 ◽

Vol 57 (1) ◽

pp. 119-127 ◽

Cited By ~ 6

Author(s):

Dennis G. Garratt ◽

Pierre Beaulieu

Keyword(s):

Double Bond ◽

Chloride Solution ◽

Methylene Chloride ◽

Effective Mechanism ◽

Substituent Group ◽

Methylene Chloride Solution ◽

Inductive Effects ◽

Allene System

The reaction of 2,4-dinitrobenzenesulphenyl chloride with eight alkyl 1,3-disubstituted allenes in methylene chloride solution has been investigated. In contrast to earlier reports, attack by sulphur is found to occur exclusively at the central allenic carbon. The direction of approach of sulphenyl chloride leads preferentially to the formation of the E isomers in accord with the concept of steric approach control. The ratio of E to Z alkene is found to increase as the bulk of the substituent group cis to the arylthio group increases. We observe, however, very little regioselectivity with respect to which of the mutually perpendicular π bonds of the allene system is attacked, suggesting the presence of an effective mechanism for transmission of inductive effects to the more distant double bond.

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Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex

The Journal of Cell Biology ◽

10.1083/jcb.200106104 ◽

2001 ◽

Vol 155 (3) ◽

pp. 369-380 ◽

Cited By ~ 90

Author(s):

Hein Sprong ◽

Sophie Degroote ◽

Tijs Claessens ◽

Judith van Drunen ◽

Viola Oorschot ◽

...

Keyword(s):

Golgi Complex ◽

Protein Transport ◽

Transmembrane Domain ◽

Direct Pathway ◽

Mouse Melanoma Cell ◽

Multicellular Organisms ◽

Rate Limiting ◽

Tyrosinase Related Protein ◽

Mouse Melanoma Cell Line

A;lthough glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.

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