Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science

Chemical Reactions and Isotopes

Works Count: 85269

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This cluster of papers focuses on the use of deuterium and tritium labeling, hydrogen isotope exchange, and catalysis in drug discovery and development. It explores applications in medicinal chemistry, metabolism studies, and the incorporation of deuterium into pharmaceutical compounds. The research also highlights the use of iridium-catalyzed reactions and the impact of deuterium substitution on drug pharmacokinetics.

Keywords

Deuterium; Drug Discovery; Isotope Chemistry; Medicinal Chemistry; Catalysis; Pharmaceutical Compounds; Tritium Labeling; Hydrogen Isotope Exchange; Metabolism Studies; Iridium-Catalyzed Reactions

Hepatic Triphosphopyridine Nucleotide-Cytochrome c Reductase: Isolation, Characterization, and Kinetic Studies

1962-08-01

Alvah H. Phillips , Robert Langdon

The biological chemistry of the elements: the inorganic chemistry of life

1992-09-01

J. J. R. Fraústo da Silva , Richard J. Williams

Part 1 The chemical and physical factors controlling the elements of life: the chemical elements in biology the principles of the chemical uptake and speciation of the elements in biology … Part 1 The chemical and physical factors controlling the elements of life: the chemical elements in biology the principles of the chemical uptake and speciation of the elements in biology physical separation of the elements - compartments and zones in biology kinetic considerations of element reactions energy in biological systems and hydrogen biochemistry the functional value of the chemical elements in biological systems. Part 2 The roles of individual elements in biology: the role of biological macromolecules and polymers sodium and potassium - osmotic control, electrolyte equilibria and currents magnesium - primary metabolism and polynucleotide structures calcium - controls and triggers zinc - Lewis acid catalysis and regulation non-haem iron redox reactions and controls haem iron - coupled redox reactions manganese copper - extracellular redox reactions and matrix formation nickel and cobalt - primitive hydrogen and organmetallic biochemistry molybdenum and vanadium - nitrogen fixation and extracellular oxygen transfer phosphorus and silicon - condensation reactions of non-metals redox non-metals - sulphur, selenium and halogens. Part 3 The co-operative interaction of elements in living systems: biomineralization and shape homeostasis and morphogenesis man's interference in element distribution - medicines and pollutants.

Stereological Principles for Morphometry in Electron Microscopic Cytology

1969-01-01

Ewald R. Weibel

[57] Sequencing end-labeled DNA with base-specific chemical cleavages

1980-01-01

Allan M. Maxam , Walter Gilbert

The Organic Chemistry of Drug Design and Drug Action

1992-01-01

Richard B. Silverman

Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms

1991-07-01

T D Porter , Minor J. Coon

The Magnitude of the Primary Kinetic Isotope Effect for Compounds of Hydrogen and Deuterium.

1961-06-01

F. H. Westheimer

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Magnitude of the Primary Kinetic Isotope Effect for Compounds of Hydrogen and Deuterium.F. H. WestheimerCite this: Chem. Rev. 1961, 61, 3, 265–273Publication Date (Print):June 1, 1961Publication … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Magnitude of the Primary Kinetic Isotope Effect for Compounds of Hydrogen and Deuterium.F. H. WestheimerCite this: Chem. Rev. 1961, 61, 3, 265–273Publication Date (Print):June 1, 1961Publication History Published online1 May 2002Published inissue 1 June 1961https://pubs.acs.org/doi/10.1021/cr60211a004https://doi.org/10.1021/cr60211a004research-articleACS PublicationsRequest reuse permissionsArticle Views7733Altmetric-Citations680LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Hydrogen: An Overview

2007-10-01

Wolfgang Lubitz , William Tumas

ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTHydrogen: An OverviewWolfgang Lubitz and William TumasView Author Information Max-Planck-Institut für Bioanorganische Chemie, Mülheim Los Alamos National Laboratory Cite this: Chem. Rev. 2007, 107, 10, 3900–3903Publication Date … ADVERTISEMENT RETURN TO ISSUEPREVEditorialNEXTHydrogen: An OverviewWolfgang Lubitz and William TumasView Author Information Max-Planck-Institut für Bioanorganische Chemie, Mülheim Los Alamos National Laboratory Cite this: Chem. Rev. 2007, 107, 10, 3900–3903Publication Date (Web):October 10, 2007Publication History Published online10 October 2007Published inissue 1 October 2007https://pubs.acs.org/doi/10.1021/cr050200zhttps://doi.org/10.1021/cr050200zeditorialACS PublicationsCopyright © 2007 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views33156Altmetric-Citations624LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (87 KB) Get e-AlertscloseSUBJECTS:Catalysts,Energy,Fuel cells,Hydrogen,Peptides and proteins Get e-Alerts

Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode

1965-02-01

Barnett Rosenberg , Loretta Van Camp , Thomas Krigas

TRITIUM-LABELING BY EXPOSURE OF ORGANIC COMPOUNDS TO TRITIUM GAS1

1957-02-01

K. E. Wilzbach

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTRITIUM-LABELING BY EXPOSURE OF ORGANIC COMPOUNDS TO TRITIUM GAS1Kenneth E. WilzbachCite this: J. Am. Chem. Soc. 1957, 79, 4, 1013Publication Date (Print):February 1, 1957Publication History Published online1 … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTRITIUM-LABELING BY EXPOSURE OF ORGANIC COMPOUNDS TO TRITIUM GAS1Kenneth E. WilzbachCite this: J. Am. Chem. Soc. 1957, 79, 4, 1013Publication Date (Print):February 1, 1957Publication History Published online1 May 2002Published inissue 1 February 1957https://pubs.acs.org/doi/10.1021/ja01561a078https://doi.org/10.1021/ja01561a078research-articleACS PublicationsRequest reuse permissionsArticle Views401Altmetric-Citations534LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Autoradiographic Study of Cell Migration during Histogenesis of Cerebral Cortex in the Mouse

1961-11-01

Jay Angevine , Richard L. Sidman

Estrogen-Receptor Interaction

1973-10-12

Elwood V. Jensen , Eugene R. DeSombre

The interaction of estradiol with uterine cells involves the association of the hormone with an extranuclear receptor protein, followed by temperature dependent translocation of the resulting complex to the nucleus. … The interaction of estradiol with uterine cells involves the association of the hormone with an extranuclear receptor protein, followed by temperature dependent translocation of the resulting complex to the nucleus. During this process, the steroid binding unit of the protein undergoes an alteration, called "receptor transformation," that can be recognized by an increase in its sedimentation rate from 3.8 S to 5.2 S, and by its acquisition of the ability to bind to isolated uterine nuclei and to alleviate a tissue specific deficiency in the RNA synthesizing capacity of such nuclei. Receptor transformation can be effected in the absence of nuclei by warming uterine cytosol with estradiol. This preparation of transformed complex resembles that extracted from nuclei both in its sedimentation rate (5.3 S ) and in its ability to bind to uterine nuclei and augment RNA synthesis, properties that are not shown by the native complex. It is proposed that receptor transformation is an important step in estrogen action and that a principal role of the hormone is to induce conversion of the receptor protein to a biochemically functional form.

Exchange reactions and electron transfer reactions including isotopic exchange. Theory of oxidation-reduction reactions involving electron transfer. Part 4.—A statistical-mechanical basis for treating contributions from solvent, ligands, and inert salt

1960-01-01

R. A. Marcus

R. A. Marcus, Discuss. Faraday Soc., 1960, 29, 21 DOI: 10.1039/DF9602900021 R. A. Marcus, Discuss. Faraday Soc., 1960, 29, 21 DOI: 10.1039/DF9602900021

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Optimal conditions for mutagenesis by N-methyl-N′-nitro-N-nitrosoguanidine in escherichia coli K12

1965-03-01

Edward A. Adelberg , Morton Mandel , Grace Chein Ching Chen

Effects of Cytochalasins on Mammalian Cells

1967-01-01

S. B. CARTER

Calculation of Equilibrium Constants for Isotopic Exchange Reactions

1947-05-01

Jacob Bigeleisen , Maria Goeppert Mayer

It is pointed out that the possibility of chemical separation of isotopes is a quantum effect. This permits a direct calculation of the difference in the free energies of two … It is pointed out that the possibility of chemical separation of isotopes is a quantum effect. This permits a direct calculation of the difference in the free energies of two isotopic molecules. Tables and approximation methods are given which permit a rapid calculation of equilibrium constants if the frequency shifts on isotopic substitution are known. Several applications are discussed.

Stomach NO synthesis

1994-04-01

Nigel Benjamin , Fionnuala O'Driscoll , Hamish Dougall +4 more

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Colorimetric Methods of Analyses

1950-02-01

Foster Dee Snell , Cornelia T. Snell

Colorimetric methods of analysis , Colorimetric methods of analysis , کتابخانه مرکزی دانشگاه علوم پزشکی تهران Colorimetric methods of analysis , Colorimetric methods of analysis , کتابخانه مرکزی دانشگاه علوم پزشکی تهران

Techniques of Autoradiography

1967-12-18

Renato Baserga

This book describes in detail the techniques of autoradiography as applied to biology and medicine. The last book on the subject was published by G. A. Boyd in 1955, and … This book describes in detail the techniques of autoradiography as applied to biology and medicine. The last book on the subject was published by G. A. Boyd in 1955, and the progress made by autoradiography in the past 12 years has been such as to make Boyd's book obsolete. In the circumstances, the effort of Dr. Rogers is welcomed by all investigators using autoradiography to study life processes. The book includes 18 chapters dealing variously with both the theory and practice of autoradiography. A description of nuclear emulsions and of the photographic process is given in readable form, and after treating the problem of autoradiographic resolution and efficiency, Dr. Rogers describes in more detail some of the techniques in use. These include the dip-coating technique, the stripping-film technique, and autoradiography with the electron microscope. Two subjects are treated in more detail than can be found in articles or chapters dealing

Regeneration of nicotinamide cofactors for use in organic synthesis

1987-03-01

H. Keith Chenault , George M. Whitesides

PHOSPHATE BOUND TO HISTIDINE IN A PROTEIN AS AN INTERMEDIATE IN A NOVEL PHOSPHO-TRANSFERASE SYSTEM

1964-10-01

W. Kündig , Sudhamoy Ghosh , Saul Roseman

Mammalian tissues contain a kinase involved in the intermediary metabolism of the sialic acids.1' 2 This enzyme has been extensively purified,3 studied in detail, and catalyzes the following reaction: N-Acyl-D-mannosamine … Mammalian tissues contain a kinase involved in the intermediary metabolism of the sialic acids.1' 2 This enzyme has been extensively purified,3 studied in detail, and catalyzes the following reaction: N-Acyl-D-mannosamine + ATP Mg++ N-Acyl-D-mannosamine-6-P + ADP.To determine whether this kinase occurred in bacteria, such as Aerobacter cloacae and Escherichia coli K235,4 that metabolize N-acetyl-D-mannosamine, extracts of these organisms were examined and found to contain a novel phospho-transferase system.The system obtained from E. coli K235 consisted of two enzymes, I and II, and a histidine-containing, heat- stable protein (HPr).The sequence of reactions is: I Phosphoenolypyruvate (PEP) + HPr Mg+ Phospho-histidine- protein (P-HPr) + Pyruvate (A) P-HPr + Hexose -., -Hexose-6-P + HPr (B)PEP + Hexose M Hexose-6-P + Pyruvate (A+B)The intermediate in the system, P-HPr, is protein-bound phosphohistidine.Materials and Methods.-Unlessotherwise specified, all materials were obtained from comi- mercial sources.Previously published methods', 6 were used for the preparation, separation, and characterization of C"1-and C'4-hexosamines, N-acylhexosamines, the corresponding 6-phosphate esters, and for the periodate oxidation of the esters and the characterization of glycolaldehyde- phosphate.The following compounds were prepared as described: P-histidine,6 N-phospho- glycine,7 phosphoramidate,8 and PEP."An essential substrate for these experiments, P32-PEP was prepared enzymatically by a published procedure'0 and with the invaluable help of Dr. M. F. Utter and Mr. Douglas Kerr,-to whom we are most grateful."The P32-PEP (5-10 ,umoles per experiment) contained 200-400 c of P8a per ,umole and was purified by ion-exchange chromatog- raphy; paper chromatography and electrophoresis indicated that it was homogeneous.It was diluted with unlabeled PEP prior to use.. Purification of enzymes I, and II, and HPr: The organism, E. coli K235, was grown to the sta- cionary phase in Todd-Hewitt (Difco) broth supplemented with 1.5% glucose in a New Brunswick fermentor.Maximum yields of the phospho-transferase system were obtained when the culture was stirred during growth but without passage of air through the sparger.After washing with 1% KCl solution, the wet cell paste was stored at -18°.The cells were ruptured by sonic oscilla- tion following suspension in 0.025 M phosphate buffer, pH 7.6 (containing 0.1% 2-mercapto- ethanol and 10-3 M EDTA when enzymes I and II were desired).After centrifugation, the supernatant fluid (crude extract) was treated with charcoal to remove HPr and fractionated for I and II as outlined in Table 1.The critical step was the Qy alumina gel treatment since I was adsorbed while II was not; after washing the gel with 0.01 and 0.05 M phosphate buffers, pH 7.6, I was eluted with 0.10 M buffer.These data suggest that both enzymes were purified approximately 300-fold.Since we have not yet determined which enzyme, I or II, was present at rate-linmiting concentrations prior to their separation, the purification factor is cor- rect for only one of these enzymes, and is not known for the other.However, the availability of the purified enzymes I and II will now permit accurate analysis for each enzyme.

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Mammary Cancer Induced by a Single Feeding of Polynuclear Hydrocarbons, and its Suppression

1961-01-01

Charles Huggins , LORRAINE C. GRAND , Filomena P. Brillantes

Stereotaxic Apparatus for Operations on the Human Brain

1947-10-10

E. A. Spiegel , H. T. Wycis , María Paula Marks +1 more

Purpose: Head and neck cancer (HNC) is the sixth most common cancer worldwide with a 5-year survival rate of less than 50%. The PI3K/AKT/mTOR signaling pathway is frequently implicated in … Purpose: Head and neck cancer (HNC) is the sixth most common cancer worldwide with a 5-year survival rate of less than 50%. The PI3K/AKT/mTOR signaling pathway is frequently implicated in HNC. Recently, IQ motif–containing GTPase-activating protein 1 (IQGAP1) was discovered to scaffold the PI3K/AKT signaling pathway. IQGAP1 gene expression is increased in HNC, raising the hypothesis that IQGAP1 contributes to HNC. Experimental Design: We performed a combination of in vitro studies using human cancer cell lines treated with a cell-permeable peptide that interferes with IQGAP1′s ability to bind to PI3K, and in vivo studies utilizing mice genetically knocked out for the Iqgap1 (Iqgap1−/−). In vivo EGF stimulation assays were used to evaluate PI3K signaling. To study the role of IQGAP1 in HNC, we used a well-validated mouse model that drives HNC via a synthetic oral carcinogen, 4-nitroquinoline 1-oxide (4NQO). Results: IQGAP1 is necessary for efficient PI3K signaling in vitro and in vivo. Disruption of IQGAP1-scaffolded PI3K/AKT signaling reduced HNC cell survival. Iqgap1−/− mice had significantly lower cancer incidences, lesser disease severity, and fewer cancer foci. IQGAP1 protein levels were increased in HNC arising in Iqgap1+/+ mice. The level of PI3K signaling in 4NQO-induced HNC arising in Iqgap1−/− mice was significantly reduced, consistent with the hypothesis that IQGAP1 contributes to HNC at least partly through PI3K signaling. High IQGAP1 expression correlated with reduced survival, and high pS6 levels correlated with high IQGAP1 levels in patients with HNC. Conclusions: These data demonstrate that IQGAP1 contributes to head and neck carcinogenesis.

RELEASE OF ULTRAVIOLET LIGHT-INDUCED THYMINE DIMERS FROM DNA IN E. COLI K-12

1964-02-01

Richard P. Boyce , Paul Howard-Flanders

The fate of thymine dimers in DNA during incubation after uv light irradiation was studied in two strains of E. coli K-12. One was a multiply auxotrophic strain, AB1157, and … The fate of thymine dimers in DNA during incubation after uv light irradiation was studied in two strains of E. coli K-12. One was a multiply auxotrophic strain, AB1157, and the other was a uv-sensitive mutant, AB1886, derived from it. Strain AB1886 is unable to reactivate uv-irradiated Tl phage and is known to have a mutation at the uvrA locus. Cells were labeled in their DNA by growth with H/sup 3/thymidine, exposed to uv light, incubated in enriched minimal medium, and extracted with cold trichloroacetic acid. The acid precipitate and soluble fractions were hydrolyzed in hot acid, and the products were separated by paper chromatography. Thymine dimers were identified in the acid-insoluble fractions from both strains before incubation. During incubation thymine dimers were released into the acid-soluble fraction in the parental strain, AB1157, but not in the uv-sensitive strain AB1886. It is concluded that thymine dimers are excised from the DNA during the reactivation process in the uvr/sup +/ strain and that the sensitive uvr/sup -/ strain cannot do this. These findings suggest that the enzymatic removal of injured bases, including thymine dimers, and the reconstruction of the DNA from information on the complementary strand may be an important biologicalmore » mechanism for the preservation of DNA. (auth)« less

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Asymmetric ene reactions in organic synthesis

1992-07-01

Koichi Mikami , Masaki Shimizu

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric ene reactions in organic synthesisKoichi Mikami and Masaki ShimizuCite this: Chem. Rev. 1992, 92, 5, 1021–1050Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAsymmetric ene reactions in organic synthesisKoichi Mikami and Masaki ShimizuCite this: Chem. Rev. 1992, 92, 5, 1021–1050Publication Date (Print):July 1, 1992Publication History Published online1 May 2002Published inissue 1 July 1992https://pubs.acs.org/doi/10.1021/cr00013a014https://doi.org/10.1021/cr00013a014research-articleACS PublicationsRequest reuse permissionsArticle Views5589Altmetric-Citations573LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Vinylation of Grignard reagents. Catalysis by iron

1971-03-01

Masuhiko Tamura , Jay K. Kochi

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVinylation of Grignard reagents. Catalysis by ironMasuhiko Tamura and Jay K. KochiCite this: J. Am. Chem. Soc. 1971, 93, 6, 1487–1489Publication Date (Print):March 1, 1971Publication History Published … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVinylation of Grignard reagents. Catalysis by ironMasuhiko Tamura and Jay K. KochiCite this: J. Am. Chem. Soc. 1971, 93, 6, 1487–1489Publication Date (Print):March 1, 1971Publication History Published online1 May 2002Published inissue 1 March 1971https://pubs.acs.org/doi/10.1021/ja00735a030https://doi.org/10.1021/ja00735a030research-articleACS PublicationsRequest reuse permissionsArticle Views5610Altmetric-Citations542LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

A simplified radiometric assay for plasma norepinephrine and epinephrine

1973-02-01

Philip G. Passon , Jacob D. Peuler

A study of the genetic material determining an enzyme activity in Pneumococcus

1960-04-01

Sanford A. Lacks , Rollin D. Hotchkiss

Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis

1959-03-31

Carl W. Gottschalk , Margaret Mylle

The osmolality was determined of fluid collected by micropuncture from proximal and distal convolutions, loops of Henle, collecting ducts and vasa recta of kidneys of various rodents with and without … The osmolality was determined of fluid collected by micropuncture from proximal and distal convolutions, loops of Henle, collecting ducts and vasa recta of kidneys of various rodents with and without osmotic diuresis. Proximal tubular fluid was isosmotic; in the presence of antidiuretic hormone, early distal fluid was hypo-osmotic due to the prior reabsorption of sodium chloride, and late distal fluid again isosmotic. The hyperosmotic concentration of the urine is established in the collecting ducts, apparently as a consequence, in part at least, of the hyperosmotic reabsorption of sodium chloride in the loops of Henle. Fluid from the bends of loops of Henle, and from collecting ducts and vasa recta at the same level were equally hyperosmotic, consistent with the hypothesis that the mammalian nephron functions as a countercurrent multiplier system. The vasa recta are believed to play an important role in the concentration of the urine by functioning as countercurrent diffusion exchangers.

Parahydrogen and synthesis allow dramatically enhanced nuclear alignment

1987-09-01

Clifford R. Bowers , D. P. Weitekamp

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTParahydrogen and synthesis allow dramatically enhanced nuclear alignmentC. Russell Bowers and D. P. WeitekampCite this: J. Am. Chem. Soc. 1987, 109, 18, 5541–5542Publication Date (Print):September 1, 1987Publication … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTParahydrogen and synthesis allow dramatically enhanced nuclear alignmentC. Russell Bowers and D. P. WeitekampCite this: J. Am. Chem. Soc. 1987, 109, 18, 5541–5542Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://pubs.acs.org/doi/10.1021/ja00252a049https://doi.org/10.1021/ja00252a049research-articleACS PublicationsRequest reuse permissionsArticle Views2698Altmetric-Citations830LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

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THE ORGANIZATION AND DUPLICATION OF CHROMOSOMES AS REVEALED BY AUTORADIOGRAPHIC STUDIES USING TRITIUM-LABELED THYMIDINEE

1957-01-15

J. Herbert Taylor , Philip S. Woods , Walter L. Hughes

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THE TAGGING OF RED CELLS AND PLASMA PROTEINS WITH RADIOACTIVE CHROMIUM 1

1950-12-01

Seymour J. Gray , Kenneth Sterling

In preparation for the present study, arc spectrography 3 was used to demonstrate the presence of trace amounts of chromium in human tissues, including the blood. Tissue analyses were performed … In preparation for the present study, arc spectrography 3 was used to demonstrate the presence of trace amounts of chromium in human tissues, including the blood. Tissue analyses were performed on samples of normal human blood by means of a colorimetric method (2) with the finding of mean values of 20 y % for packed red cells and 14 y % for plasma. The present report is concerned with a new biological tracer, radioactive chromium (Cr51), which is bound by the red cells and plasma proteins. Both anionic hexavalent (Na2Cr51O4) and cationic trivalent (Cr51Cl3) states of the element have been studied.

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The Renaissance of H/D Exchange

2007-09-21

Jens Atzrodt , Volker Derdau , Thorsten Fey +1 more

The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass … The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass spectrometry or to help elucidate mechanistic theories. Access to these deuterated compounds takes place significantly more efficiently and more cost effectively by exchange of hydrogen by deuterium in the target molecule than by classical synthesis. This Review will concentrate on the preparative application of the H/D-exchange reaction in the preparation of deuterium-labeled compounds. Advances over the last ten years are brought together and critically evaluated.

Inhibition of Access of Bound Somatomedin to Membrane Receptor and Immunobinding Sites: A Comparison of Radioreceptor and Radioimmunoassay of Somatomedin in Native and Acid-Ethanol-Extracted Serum*

1980-10-01

William H. Daughaday , Ida K. Mariz , Sandra L. Blethen

No agreement exists concerning the necessity for extracting serum somatomedin (Sm) before radioreceptor assay (RRA) and RIA. We have developed a simplified system of Sm extraction which has permitted a … No agreement exists concerning the necessity for extracting serum somatomedin (Sm) before radioreceptor assay (RRA) and RIA. We have developed a simplified system of Sm extraction which has permitted a quantitative comparison of native and extracted Sm. To 0.8 ml of a mixture of 87.5% ethanol and 12.5% 2 N HC1, 0.2 ml serum is added. After centrifugation, 0.5 ml supernatant is neutralized with 0.2 ml 0.855 M Tris base (XT). Recovery of added 125I-labeled insulin-like growth factor I ([125I]IGF-I) was nearly quantitative. Neutral gel filtration studies established that virtually all of the binding complex was removed by acid-ethanol precipitation. The addition of 100 µl Tris-neutralized acid-ethanol buffer (AE B) to the [125I]IGF-I human placental membrane RRA produced an insignificant shift in the displacement curve with partially purified IGF reference preparation; the shift of the [125I]Sm C RIA displacement curve was greater but did not prevent accurate measurement when AE B was added to blank and standard tubes. When partially purified IGF was added to serum and extracted promptly with acid-ethanol, the added IGF was recovered completely in the extract, but when extraction was delayed until after 16 h of incubation at 4 C, there was poor recovery of added IGF, as determined by RRA. However, there appeared to be a similar recovery of endogenous Sms. The loss of added IGF was prevented by the addition of aprotinin. The RRA of XT in 9 normal sera gave results which were 2.72 ± 0.32 times higher than those obtained by direct RRA on native sera; the fold increment was 2.96 ± 0.37 when the measurements were made by Sm C RIA. Five sera from patients with hypopituitarism gave results with the RRA of XT which were only 1.12 ± 0.30 times greater than those obtained with direct assays on serum; the increment with RIA was 1.64 ± 0.23. The results of RRA on XTs in 34 sera from normal individuals, 18 patients with clinical GH deficiency, and 8 patients with acromegaly correlated well with the known GH status. We conclude that although direct serum Sm RRAs and RIAs have provided much useful information, these assays do not quantitatively measure the Sm content of serum. A simplified acid-ethanol extraction permits convenient and accurate measurement of total Sm. We suggest that direct RIA and RRA of Sm measure predominantly bound Sm. The reported lack of parallelism with equilibrium assays of native serum and the failure of quantitative recovery of Sm described here may be the result of steric and other factors which modify access of the Sm serum binding protein complex to membrane and immunobinding sites.

APPLICATION OF STEADY STATE KINETICS TO THE ESTIMATION OF SYNTHESIS RATE AND TURNOVER TIME OF TISSUE CATECHOLAMINES

1966-12-01

B.B. Brodie , E. Costa , A Dlabac +2 more

A method of measuring the rate of synthesis of catecholamines in various tissues takes advantage of the steady state relationship in which the rate of catecholamine formation is equal to … A method of measuring the rate of synthesis of catecholamines in various tissues takes advantage of the steady state relationship in which the rate of catecholamine formation is equal to the rate of efflux. After tyrosine hydroxylase is blocked with α-methyltyrosine, the brain levels of norepinephrine (NE) and dopamine and the NE levels in various peripheral tissues of rats and rabbits decline exponentially. The rate of synthesis of the catecholamines is calculated from the product of the rate constant of amine decline and the normal catecholamine level. The value for heart NE yielded by this method is almost identical with that obtained from the decline in radioactivity after labeling with dl -H3-NE. The application of this method to studies in the rat shows that the turnover time for NE in heart, salivary gland and iris is about 12 hr, compared to 6 hr for brain NE, 3 hr for brain dopamine and 2 hr for NE in the cervical sympathetic ganglia. In the rabbit hypothalamus, NE is formed five times more rapidly than in the midbrain, though the turnover times are almost identical. This suggests that the rate of synthesis might be similar in each adrenergic unit and that variations in rates of synthesis in different brain areas are a function of the number of neurons per gram of tissue.

Using Deuterium in Drug Discovery: Leaving the Label in the Drug

2013-12-02

Thomas G. Gant

Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its utility in mechanistic, spectroscopic, and tracer studies. In fact, well-known applications utilizing deuterium exist within every subdiscipline … Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its utility in mechanistic, spectroscopic, and tracer studies. In fact, well-known applications utilizing deuterium exist within every subdiscipline in pharmaceutical discovery and development. Recent emphasis on incorporation of deuterium into the active pharmaceutical ingredient has come about as a result of inquiries into the potential for substantial benefits of the deuterium kinetic isotope effect on the safety and disposition of the drug substance. This Perspective traces the author's experience in reviving and expanding this potential utility, first suggested many decades prior by the discoverer of this, the simplest of all isotopes.

Microtechnical Demonstration of Phosphatase in Tissue Sections.

1939-10-01

George Gömöri

In preliminary experiments the phosphatase activity of aqueous extracts of dog kidney cortex made (a) of fresh ground tissue, (b) of ground tissue dehydrated with several changes of 95% and … In preliminary experiments the phosphatase activity of aqueous extracts of dog kidney cortex made (a) of fresh ground tissue, (b) of ground tissue dehydrated with several changes of 95% and absolute alcohol, (c) of dehydrated ground tissue exposed to 56°C for one hour was determined by the Berenblum-Chain modification of Kay's method. These experiments have shown that phosphatase is not destroyed either by alcohol or by exposure to 56°C in completely dehydrated state, the maximum decrease in activity observed having amounted to less than 20%. Moreover, purification of phosphatase by alcohol precipitation has been successfully used by Mart-land and Robison. It appeared possible to demonstrate phosphatase in celloidin or paraffin sections on the basis of the following principle: If tissue sections containing active phosphatase are incubated with a solution of sodium glycerophosphate or of some other suitable ester-phosphate, such as hexose-phosphate or nucleinate, at a suitable pH, at the sites where phosphatase is present, PO4 ions will be split off. These ions may be trapped at the spot by the salts of metals whose phosphates are insoluble. A precipitate of insoluble phosphate forms which, if visible, or made visible, indicates the presence of phosphatase. A useable technic has been worked out on the basis of this principle.Fixation. Phosphatase is dissolved or destroyed by most of the routine fixatives. In alcohol, however, it is preserved for many weeks at least. Thin slices of fresh tissue should be fixed in 95% alcohol for about one day.Unfortunately, decalcification is impossible, because all acids destroy phosphatase completely.Embedding. Both celloidin and paraffin embedding is suitable. If the tissue is well dehydrated, exposure to paraffin at 56 to 60°C for 2 hours will do no harm.

Cytochrome P450 Structure, Function and Clinical Significance: A Review

2017-02-23

Manikandan Palrasu , Siddavaram Nagini

Background: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is … Background: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism- based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system. Predictions based on in silico analyses followed by validation have identified several microRNAs that regulate CYPs. Genetic polymorphisms and epigenetic changes in CYP genes may be responsible for inter-individual and interethnic variations in disease susceptibility and the therapeutic efficacy of drugs. Objective: The present review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, pharmacoepigenetics and clinical significance. Conclusion: Knowledge about the substrates, inducers, and inhibitors of CYP isoforms, as well as the polymorphisms of CYP enzymes may be used as an aid by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products. Keywords: Adverse drug reactions (ADRs), cytochrome P450, drug interactions, genetic polymorphisms, microRNA, moonlighting proteins, xenobiotics.

Deuterium‐ and Tritium‐Labelled Compounds: Applications in the Life Sciences

2017-08-17

Jens Atzrodt , Volker Derdau , William J. Kerr +1 more

Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag … Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium-labelled isotopologues to study the unique mass-spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (3 H), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.

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Applications of Deuterium in Medicinal Chemistry

2019-01-14

Tracey Pirali , M. Teresa Serafini , Sarah Cargnin +1 more

The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and … The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms of metabolism-mediated toxicity, drug interactions, and low bioactivation. The use of deuterium is even broader, offering the opportunity to lower the degree of epimerization, reduce the dose of coadministered boosters, and discover compounds where deuterium is the basis for the mechanism of action. Nevertheless, designing, synthesizing, and developing a successful deuterated drug is far from straightforward, and the translation from concept to practice is often unpredictable. This Perspective provides an overview of the recent developments of deuteration, with a focus on deuterated clinical candidates, and highlights both opportunities and challenges of this strategy.

Encyclopedia of Reagents for Organic Synthesis

2001-04-15

Andrei Corbu , Stellios Arseniyadis

325.11) (reagent for diazo or nonafluorobutanesulfonylamino transfer, and as 1,3-dipole 325.11) (reagent for diazo or nonafluorobutanesulfonylamino transfer, and as 1,3-dipole

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Coumarins : biology, applications, and mode of action

1997-01-01

Richard O’Kennedy , R. D. Thornes

List of contributors. Preface. History of the Development and Applications of Coumarin and Coumarin--related Compounds (I. Weinmann). The Chemistry and Occurrence of Coumarins (G. Keating & R. Oa Kennedy). The … List of contributors. Preface. History of the Development and Applications of Coumarin and Coumarin--related Compounds (I. Weinmann). The Chemistry and Occurrence of Coumarins (G. Keating & R. Oa Kennedy). The Metabolism of Coumarin (O. Pelkonen). The Effects of Coumarin and its Metabolites on Cell Growth and Development (B. Seliger). Coumarin as an Immunomodulator (G. Zlabinger). The mode of Entry of Coumarin into Cells and its Effects on Cell--Cell Communication and Migration (K. S. Zlabinger). Coumarin in the Treatment af Lymphoedema and Other High--Protein Oedemas (J. R. Casley--Smith, J. R.Casley--Smith). Mode of Action of Coumarin in the Treatment of Thermal Injuries (N. Piller). Renal Cell Carcinoma: The Background, Rationale and Current Development of Coumarin (1,2--benzopyrone) as a Potential Therapeutic Agents (S. W. Ebbinghaus, et al.). The Potential Role of Coumarins in the Therapy of Prostate Cancer (J. Mohler, et al.). Clinical and Biological Observations Associated with Coumarins (R. Thornes). Analysis of Coumarins (D. Bogan, et al.). Coumarins -- Multifaceted Molecules with Many analytical and Other Applications (D. Cooke et al.). Suggested Modes of Action of Coumarins and Some Comments on their Significance (R. Oa Kennedy & R. Thornes). Index.

Synthesis of optically active α-amino acids

1989-01-01

Robert M. Williams

Asymmetric derivatization of glycine. Homologation of the beta-carbon. Electrophilic amination of enolates. Nucleophilic amination of alpha-substituted acids. Asymmetric Strecker syntheses. Asymmetric hydrogenation of dehydroamino acids. Enzymatic syntheses of alpha-amino acids. … Asymmetric derivatization of glycine. Homologation of the beta-carbon. Electrophilic amination of enolates. Nucleophilic amination of alpha-substituted acids. Asymmetric Strecker syntheses. Asymmetric hydrogenation of dehydroamino acids. Enzymatic syntheses of alpha-amino acids. Miscellaneous methods. Total synthesis of complex amino acids. Author index. Subject index.

Biological nitrogen removal from wastewater

1994-01-01

Udo Wiesmann

Development of a Multistage Technology for the Industrial Synthesis of the Levosimendan API and Enantiomeric Separation of Intermediates

2025-06-24

Liubov V. Sokolenko , Taras M. Sokolenko , Andrey А. Filatov +3 more | Journal of organic and pharmaceutical chemistry

A method for obtaining Levosimendan suitable for industrial application has been developed. Two literature routes for the synthesis have been evaluated. It has been found that the use of enantiopure … A method for obtaining Levosimendan suitable for industrial application has been developed. Two literature routes for the synthesis have been evaluated. It has been found that the use of enantiopure (R)-2-chloropropionyl chloride in the initial step is ineffective due to racemization at the stage of the synthesis based on the malonic ester. Instead, a reported method based on the synthesis of the Levosimendan precursor, 6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (1), from racemic 2-bromopropionyl bromide has been modified to allow for scale-up and adaptation to industrial processes. A practical resolution method has been developed to isolate the (R)-enantiomer of amine 1 from the racemic mixture with a high enantiomeric purity (the content of (R)-enantiomer is up to 99%). It has been shown that (R)-1 can be converted to Levosimendan in a high yield without the stereochemical purity loss at the chiral center.

Discovery of 2-Ethynylisoborneol as a Highly Potent Anti-seizure Agent

2025-06-23

Xianjing Zhou , Fan Fei , Ying Zhong +7 more | Journal of Medicinal Chemistry

Epilepsy is a type of severe neurological disorder that is caused by abnormal neuronal discharges. Natural D-(+)-borneol has been proven to attenuate epileptic seizures, while its potency and pharmacokinetic profiles … Epilepsy is a type of severe neurological disorder that is caused by abnormal neuronal discharges. Natural D-(+)-borneol has been proven to attenuate epileptic seizures, while its potency and pharmacokinetic profiles remain improved. In this study, optimization strategies including prodrug modification, bioisosterism, and metabolic site blocking were performed for aiming to hunt more potent antiseizure borneol derivatives. Thus, various D-(+)-borneol derivatives were prepared and subjected to in vivo antiseizure evaluation with PTZ and MES models. And compound 13 was identified as a promising candidate with favorable pharmacokinetic properties (F = 114.8%) coupled with high and broad-spectrum antiseizure potential. 13 could prolong the latency to stage 6 of the PTZ model from 285.3 to 786.5 s upon oral administration of 30 mg/kg. Mechanistically, 13 was found to ameliorate epileptic seizures via weakening the excitability of glutamatergic transmission. Overall, this work provides a new optimization strategy of borneol and a new chemical entity for epilepsy treatment.

Photoreductive Deuteration of C=N Bonds by Au/CdS Nanosheets

2025-06-20

Qiyuan Wang , Haochuan Jing , Wei Ou +7 more | ACS Catalysis

Editorial: Modern advances in direct reactions for nuclear structure

2025-06-20

A. H. Wuosmaa , S. J. Freeman , B. P. Kay | Frontiers in Physics

Erratum: “Alternative Methylated Biosignatures. I. Methyl Bromide, a Capstone Biosignature” (2022, ApJ, 938, 6)

2025-06-20

Michaela Leung , Edward W. Schwieterman , Mary N. Parenteau +1 more | The Astrophysical Journal

Advancing Isotope Labeling Technologies at AstraZeneca through Academic–Industrial Collaboration

2025-06-20

Ryan A. Bragg , Jonas Bergare , Markus Artelsmair +3 more | ACS Medicinal Chemistry Letters

Correction to “Carbodicarbene‐Stibenium Ion‐Mediated Functionalization of C(sp3)−H and C(sp)−H Bonds”

2025-06-18

| Angewandte Chemie

Correction to “Carbodicarbene‐Stibenium Ion‐Mediated Functionalization of C(sp3)−H and C(sp)−H Bonds”

2025-06-18

| Angewandte Chemie International Edition

Role of Active Site Residues and Weak Noncovalent Interactions in Substrate Positioning in N,N-Dimethylformamidase

2025-06-17

Clorice R. Reinhardt , David W. Kastner , Heather J. Kulik | Biochemistry

N,N-Dimethylformamide (DMF) is a solvent that can be metabolized naturally by DMF-utilizing microorganisms via a nonheme iron enzyme N,N-dimethylformamidase (DMFase). DMF is a small molecule with very few hydrogen bond … N,N-Dimethylformamide (DMF) is a solvent that can be metabolized naturally by DMF-utilizing microorganisms via a nonheme iron enzyme N,N-dimethylformamidase (DMFase). DMF is a small molecule with very few hydrogen bond donors or acceptors, and thus must be bound in the active site through other noncovalent interactions. We investigated the unusual protein fold, role of active site residues, and substrate positioning by performing molecular dynamics (MD) simulations and studying DMF binding. Our docking studies support idea that the DMF substrate directly coordinates the iron center through its carbonyl group, with Fe-DMF distances consistent with structures of inorganic complexes. DMF binding is predominantly stabilized by weak noncovalent interactions with nearby phenylalanine residues, which also serve to control access of solvent to the active site according to cavity analysis of crystal structures and MD snapshots. Based on noncovalent interactions sampled in our simulations and on sequence conservation, we ascribe roles to active site residues E657β, H519β, N547β, F611β, and F693β'. We perform sequence and structural alignments to identify putative DMFases and active site geometries in protein structures predicted from metagenomic DNA. These analyses suggest common conserved residues among putative DMFases and relate them to catalytic function, providing guidance for future experimental studies or characterization of new DMFases for DMF bioremediation.

Recombinant Expression of Hypericin Synthase Hyp1 in Escherichia coli and Elucidation of Its Solubility Mechanisms

2025-06-14

Fuguo Zhou , Hao Du , Jiaxin LÜ +1 more | Medical Research

Hypericin, the principal bioactive naphthodianthrone from Hypericum perforatum, exhibits broad‐spectrum antibacterial, antitumor, antidepressant and antiviral properties; however, its low natural abundance and suboptimal purity hinder large‐scale applications. In this study, … Hypericin, the principal bioactive naphthodianthrone from Hypericum perforatum, exhibits broad‐spectrum antibacterial, antitumor, antidepressant and antiviral properties; however, its low natural abundance and suboptimal purity hinder large‐scale applications. In this study, two hypericin synthase isoforms, Hyp1A and Hyp1B, were recombinantly expressed in Escherichia coli. Following IPTG induction, Hyp1A accumulated to 94.2 μg·g-1 wet cell mass, which increased to 1.41 mg·g-1 upon fusion with a solubility‐enhancing tag. In contrast, Hyp1B achieved 7.53 mg·g-1 wet cells without modification, highlighting distinct expression phenotypes. Molecular dynamics simulations revealed that Hyp1A harbors a higher proportion of random coil and fewer α-helices relative to Hyp1B, correlating with reduced structural stability. In vitro assays confirmed that Hyp1B catalyzes emodin dimerization to hypericin, albeit with limited activity under current conditions. Collectively, these findings demonstrate the feasibility of emodin‐to‐hypericin bioconversion and establish a foundation for engineering more efficient biosynthetic processes and clinical application of hypericin.

Anomalous long-range hard-wall repulsion between polymers in solvent mixtures and its implication for biomolecular condensates

2025-06-13

NULL AUTHOR_ID | Physical Review Letters

The Work of Carlo Garosi: a Parallel History of the Discovery of Tritium

2025-06-12

Benedetto Pietro Casu , Duccio Tatini | Substantia

The advent of "New Physics" at the beginning of the XX century ignited a transformative era for Nuclear Physics, characterized by a dramatic growth of its knowledge and boundaries. The … The advent of "New Physics" at the beginning of the XX century ignited a transformative era for Nuclear Physics, characterized by a dramatic growth of its knowledge and boundaries. The existence of isotopes, the discovery of neutrons and the advancement of experimental techniques all conjured groundbreaking discoveries, where experimental physicists were at the forefront of developments. The discovery of tritium, the hydrogen isotope of mass number 3, is among the most sought-after results in the 1930s, and we present evidence of how Carlo Garosi, an Italian pharmacist, made significant yet unacknowledged contributions in 1936. By recognizing the importance of the Oliphant, Harteck and Rutherford experiment of 1934, Garosi correctly identified the heavy atom discovered as an isotope of hydrogen. This paper begins with the recapitulation of both the philosophical and scientific roots of his theory, showing how he critically engaged with older theories, such as Prout’s 19th-century atomic theory, and integrated more recent works from international sources in original ways. Garosi proposed a unique interpretation of the Periodic Table, engaging in a critical review of the notion of how Helium is a result of the fusion of 4 Hydrogen atoms, and he explains the progression from one chemical element to another in terms of interactions among hydrogen, deuterium and tritium. By revisiting this seemingly peripheral event, we underscore its broader significance as a testament to the resilience and ingenuity of scientists journeying amid rising geopolitical tensions.

New nitrogen allotrope created at last

2025-06-11

Bethany Halford | C&EN Global Enterprise

FDA approves a c-MET-targeted ADC for lung cancer

2025-06-10

Asher Mullard | Nature Reviews Drug Discovery

Latest News: More dual labelled medicines transition to sole names

2025-06-10

| Australian Prescriber

Base-Promoted Iridium-Catalyzed Deuteration and C–H Bond Activation of N-Heterocycles

2025-06-05

Ben. J. Tickner , Claire Condon , Victoria Annis +3 more | The Journal of Organic Chemistry

Hydrogen isotope exchange (HIE) of N-heterocycles is highly important in synthesis, where it is often used to prepare probes suitable for pharmaceutical studies. In this work, we show that pharmaceuticals … Hydrogen isotope exchange (HIE) of N-heterocycles is highly important in synthesis, where it is often used to prepare probes suitable for pharmaceutical studies. In this work, we show that pharmaceuticals such as anastrozole, trimethoprim, and bisacodyl can be easily deuterated in up to 84-95%, with high site selectivity using an [IrCl(COD)(IMes)]/H2/NaOMe/methanol-d4 derived catalytic system. We studied in detail the deuteration of quinoxaline using NMR spectroscopy, mass spectrometry, and X-ray crystallography and characterized a range of C-H bond activated products that include [Ir(H)2(quinoxaline)(IMes)(κ2-μ2-C,N-quinoaxline)2Ir(H)2(quinoxaline)(IMes)]; [Ir(H)2(quinoxaline)(IMes)(κ2-μ2-C,N-quinoxaline)2Ir(Cl)(H)(quinoxaline)(IMes)]; [Ir(H)2(IMes)(κ2-μ2-C,N-quinoxaline)2Ir(H)2(IMes)]; and [Ir(H)2(IMes)(κ2-μ2-C,N-quinoxaline)2(μ2-H)Ir(H)(quinoxaline)(IMes)]. Reaction scope is demonstrated by the examination of 17 structurally diverse substrates, with functional groups spanning pyridines, quinoxalines, quinolines, purine/xanthines, triazoles, and pyrimidines. Four analogous C-H-bond-activated X-ray structures were obtained for the additional substrates. Catalytic turnover was found to dramatically increase upon the addition of NaOMe and is linked to a demonstrated role for trihydride species [Ir(H)3(COD)(IMes)] in the HIE process, with the reactive fragment {IrH(IMes)} implicated in the formation of catalytically competent dinuclear C-H bond activation products.

New ultrasound-assisted microreactor for extracting extraterrestrial biomolecules

2025-06-03

Ramzi Timoumi , Rihab Fkiri , Prince Nana Amaniampong +4 more | Ultrasonics Sonochemistry

Catalytic α‐Site‐Selective Hydrogen‐Deuterium Exchange of Benzylic Alcohols by Palladium Single‐Atom Catalyst

2025-06-02

Shuxian Li , Xiang‐Ting Min , Juan Su +4 more | Angewandte Chemie International Edition

Catalytic hydrogen-deuterium exchange (HDE) has emerged as a valuable tool for achieving site-selective deuteration and the precision labelling of bioactive molecules. Incorporation of deuterium at metabolically labile positions, enabled by … Catalytic hydrogen-deuterium exchange (HDE) has emerged as a valuable tool for achieving site-selective deuteration and the precision labelling of bioactive molecules. Incorporation of deuterium at metabolically labile positions, enabled by such methods, can potentially improve drug efficacy through the kinetic isotope effect. However, achieving precise, site-selective incorporation of deuterium at specific molecular positions remains challenging. Herein, we report a highly efficient α-site-selective HDE of benzylic alcohols via a palladium single-atom catalyst (SAC). By using the Pd SAC, exceptional activity and selectivity in HDE reactions were achieved, delivering up to 95% deuterium incorporation (D-inc.) at the α-position while effectively suppressing undesired pathways (e.g., α,β-multisite deuteration). Mechanistic investigations reveal that the Pd SAC promotes site selective HDE through two distinct surface pathways: (i) a previously unreported direct C-H bond activation and (ii) a modified borrowing hydrogen process in which high-pressure hydrogen inhibits the keto enol tautomerization, thereby largely circumvents α,β-multisite deuteration. The catalyst exhibits robust stability, reusability, and broad substrate compatibility, underscoring its potential for practical applications. This work marks a significant advance in heterogeneous single-atom catalytic methodologies for site-selective deuteration, offering a complementary solution to longstanding challenges in catalytic organic synthesis.

Treating Aggressive Brain Tumors with the Combo Bumetanide/Mebendazole: A New Cytotoxic, Anti-Invasive Network Strategy

2025-06-02

| Annals of Case Reports