DOCSLIB.ORG

Radicals and the Birth and Death of DNA

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Radicals and the Birth and Death of DNA CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 275 CHIMIA 2001,55, No.4 Chimia 55 (2001) 275-280 © Schweizerische Chemische Gesellschaft ISSN 0009-4293 Radicals and the Birth and Death of DNA Bernd Giese Abstract: Radicals have important functions in the enzymatic synthesis of deoxyribonucleotides and their destruction by antibiotics. The chemical basis for these reactions is that radicals dramatically speed up ionic reactions. Nature has developed methods to generate these radicals under mild conditions in water as solvent. The 'catalytic' effect of these reactive intermediates is described. Keywords: Bleomycin' DNA· Enzymes· Radicals· Ribonucleotide reductase 1. Introduction ics like bleomycin or OHo radicals The chemistry of these radicals was (formed during oxidative stress) cause studied in order to understand the action Radicals play an important role in biolog- the death of DNA [1]. One of the inter- of the enzyme ribonucleotide reductase ical systems [1]. Among the targets for mediates involved in these reactions is and of the antibiotic bleomycin. radical attack are nucleotides as well as the 4'-DNA radical 5, which leads to their polymers, DNA and RNA. This at- strand cleavage even in the absence of tack leads to reactive intermediates with 3. Enzymatic Synthesis of radical centers at the carbohydrates or the °2' Deoxyribose heterocyclic bases of the nucleic acids. We have studied these radicals by syn- 2. Generation of the Radicals It is known, especially from the ex- thesis of their precursors and selecti ve periments of J. Stubbe and W.A. van der generation of the reactive intermediates. We have synthesized acyl selenide 11 Donck [4], that the first step of the enzy- Of special interest are the 3'- and 4'-nu- and pivaloyl ketone 16 as precursors for matic deoxygenation of ribonucleotides cleotide radicals because they are in- the 3'-and 4'-nucleotide radicals, respec- is the homolytic cleavage of their 3'-C,H- volved in the birth and the death of DNA. tively [2][3] (Scheme 2). bond by a thiyl radical (20~21). This is a As shown in Scheme 1, the building From 11, the 3'-radicaI17 can be gen- surprising reaction, because thiols are blocks for DNA, deoxyribonucleotides 3, erated via tributyltin radicals, whereas 16 normally used to trap carbon-centered are formed in a radical deoxygenation was first incorporated into double strand- radicals, which corresponds to the re- reaction of ribonucleotides 1. The bio- ed 18, which leads to the 4'-radical 19 verse reaction 21~20. Our model exper- synthesis is catalyzed by the enzyme ri- upon photolysis (Scheme 3). iments have solved this apparent contra- bonucleotide reductase, which generates 3'-ribonucleotide radical 2 as a reactive intermediate. With the help of kinases PP PPO b PP0 b and polymerases these deoxyribonucle- ribonucleotide ------)<- q0 - otides 3 give birth to double-stranded p reductase _ scission t1 DNA, which is a very stable molecule. HO OH HO OH OH Nevertheless, its structure is destroyed 1 2 3 under radical attack, and certain antibiot- bleomycin gap •.. or - oxidative stress ·Correspondence: Prof. B. Giese Department of Chemistry University of Basel St. Johanns Ring 19 CH-4056 Basel 4 5 6 Tel.: + 4161 2671106 Fax: + 41 61 267 1105 E-Mail: [email protected] Scheme 1. Radicals as decisive reactive intermediates in the formation of deoxyribonucleotides http://www.chemie.unibas.ch/-giese/index.html and their destruction in the DNA. CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 276 CHIMIA 2001.55, NO.4 diction. It turned out that the deoxygena- tion of a radical like 21 is generally base ~BDMS0t1BZ 1. Dess-Martin H0t1 ~S~ catalyzed [2]. The slowest step of this HO 2-"""CeC12 process is the deprotonation (21~22), HO OH HO OTBDMS # OH 80% which is followed by an irreversible 7 8 9 P-C,O-bond cleavage (22~23). As a re- sult of these fast subsequent reaction steps even very small equilibrium con- 0 centrations of radical 21 can lead to an TBAF (PhO)P'CI" 2 efficient deoxygenation reaction Me2CO, AC20 PhSeH. HCI HO 'Iori"' (Scheme 4). 03• KMn04 OAe "°11OH HO 0 50% PhSe 0 55% The glutamic acid at position 441 10 11 plays the role of the general base catalyst in the enzyme. Its reaction leads to the protonated carboxylic acid in 23, which subsequently catalyzes the reduction of ketone 24 [2]. Unprotonated ketones can- not be reduced by a disulfide radical ani- "0t] _ O~O~ 1. tBuli/CeCI3(61%) 'BU't~~ on (formed by the H-atom abstraction \-.l 2. (F3CC0l20 I DMSO (85%) \-' step 23~24), but a reduction is easily OH OTBDMS OTBDMS feasible after protonation of the ketone. 12 13 14 Thus, our model studies suggest an en- zyme mechanism where acid/base cataly- sis is decisive for the chemical reactions (Scheme 5). Trapping of the 3'-radical 25 HO"}O~ DMTrO"}O~ 1. TBAF (95%) . by cystein 439 completes the synthesis of BO% IBUJ[~ 2. Ba(OHl2/ CH20 (64%) IBUJ[\-.l - the deoxyribonucleotide. o OH o 0 I In support of these conclusions, X-ray 15 P ('PrbN' 'OCH2CH2CN studies of Uhlin and Eklund have shown 16 that glutamic acid 441 is in an appropri- ate position to act as the acid/base cata- lyst [5] (Fig. 1). Scheme 2. Synthesis of the radical precursors 11 and 16. 4. Radical Induced DNA Strand Cleavage The antibiotic bleomycin generates HOiiA HO~ 4'-DNA radical 19 after binding as a met- HO al/oxygen complex to DNA and subse- OH HO OH quent H-atom abstraction [6]. We have PhSe 0 formed this 4'-nucIeotide radical by pho- 11 17 tolysis of ketone 18 and studied its chem- istry [7]. Depending upon the conditions, radical 19 leads to products 26-28 (Scheme 6). In the presence of metal oxides radi- cal 19 is oxidized to the cation, which is trapped by water and yields ketoaldehyde 26 [8]. Aerobic conditions generate peroxyl radical 32 which leads to hydroperoxide p P 33 in the presence of H-donors [9]. If the o hydroperoxide is situated within the hv 16 t ~O~ DNA strand, a Criegee rearrangement • Bu ~ 1""""A t-' \JT"""'A occurs, whereas a hydroperoxide at the end of the strand (R2 = H) undergoes a Grob fragmentation [9]. Subsequent elimination and/or hydrolysis leads to ~"'''". ~"""" glycolate 27 (Scheme 7). 18 19 The chemically most interesting reac- tion is the Orindependent cleavage of the 4'-DNA radical. In very detailed stud- Scheme 3. Generation of the 3'-ribonucleoside radical 17 and the 4'-DNA radical 19. ies using kinetic experiments [10], chem- CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 277 CHIMIA 2001, 55, NO.4 Cys439 Glu441 Cys462 Cys225 20 21 22 fast )0 Scheme 4. Schematic reaction scheme for the enzymatic deoxygenation of ribonucleotide 20. The decisive amino acids are glutamic acid 23 24 (position 441) and cystein (position 225, 439, 462). Cys439 Cys 439 general base Glu 441 •• Glu 441 catalysis Cys 462 Cys 225 Cys 462 Cys 225 21 23 Cys439 Cys 439 acid Glu 441 ------- ....•••~ Glu 441 catalysis Scheme 5. Base and acid catalyzed deoxygen- Cys 462 Cys 225 Cys 462 ation (21-723) and reduction (24-725) steps during the enzymatic synthesis of deoxyribo- 24 25 nucleotides. Fig. 1. Orientation of the ribonucleotide in the active site of ribonucleotide reductase. CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 278 CHIMIA 2001, 55, No.4 •.....-J 110 ~OCH2<_ o 27 26 19 Scheme 6. Reaction products of the 4'-DNA radical in the presence of oxidizing metal ox- ides (19~26), O (19~27), or in the absence of 28 2 radical traps (19~28). ESR MS C""gee j rearrangement ~ OR2 Scheme 7. Mechanism for the formation of 27 glycolate 27 from 4'-DNA radical 19 under aerobic conditions . ---l... .-V0~t-' OH 36 Scheme 8. Mechanism for the strand cleavage of 4'-DNA radical 19 under anaerobic condi- tions. CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 279 CHIMIA 2001,55, No, 4 ical trapping reactions [10,11], photocur- rent measurements [12], spectroscopic observations [13], as well as quantum chemical calculations [11], the existence of an enol ether radical cation 34 as cru- cial intermediate of this cleavage process was proven (Scheme 8). The fast heterolytic cleavage reaction of radical 19 demonstrates that radical centers are very efficient neighboring groups for ionic reactions [14]. Radical 19 is hydrolyzed (19~35) at least 1010 times faster than the corresponding phos- phate without a radical center at the 4'-position. The driving force is the mes- omeric stabilization of radical cation 34 and the solvation energy [11]. We have 37 utilized this neighboring group effect for the development of new photocleavable Fig. 2. Configuration of the 4'-DNA radical in double strands. linkers [15]. Another spin-off is our observation that radical cation 34 oxidizes the gua- It turns out that these modified nuc1e- these studies new insights into chemical nine bases of DNA [16]. This induces otides are excellent probes to determine reactions can also be gained. Examina- long-distance charge transfer through the contact sites between the growing tion of the radical-induced 'birth' and DNA that we are studying in detail. We DNA strand and the enzyme. The rate of 'death' of DNA has led to the surprising have been able to show that long-distance each polymerization step can be meas- chemical result that radicals are very effi- charge transport through DNA is possible ured, and a site of close contact between cient neighboring groups for ionic reac- and that it occurs in a multistep hopping enzyme and DNA is recognized by its tions. process [17]. slow chain elongation [19] (Fig. 4). Strand cleavage of the 4'-DNA radical Acknowledgments 19 can be prevented by H-atom donors.
Load more

Recommended publications
  • Sulfur-Containing Radicals: from EPR Spectroscopic Studies to Synthetic Methodology
    Sulfur-containing Radicals: From EPR Spectroscopic Studies to Synthetic Methodology A Thesis Presented to the University of London in Partial Fulfilment of the Requirements for the Degree of Doctor of Philosophy Alistair John Fielding February 2002 Christopher Ingold Laboratories Department of Chemistry University College London London WCIH OAJ UCL ProQuest Number: 10015687 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10015687 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 7 believe a leaf of grass is no less than the journey-work of the stars. ” Walt Whitman This thesis is dedicated to my late Auntie, Doreen Latter. 1930-2001 ABSTRACT A variety of novel homochiral silanethiols have been prepared and investigated as polarity-reversal catalysts for the enantioselective hydrosilylation of a prochiral alkene. The enantiomeric excesses of the products were disappointingly small. A computer modelling procedure, based on molecular mechanics, was applied in order to understand the results and quantitative agreement with experiment was reasonably good. Silanethiols have been oxidised to the corresponding disulfides and these have been investigated as photochemical sources of silanethiyl radicals.
    [Show full text]
  • Acscatal.0C01923.Pdf
    This is a repository copy of Phosphoranyl Radical Fragmentation Reactions Driven by Photoredox Catalysis. White Rose Research Online URL for this paper: https://eprints.whiterose.ac.uk/163811/ Version: Published Version Article: Rossi-Ashton, James A., Clarke, Aimee K., Unsworth, William P. orcid.org/0000-0002- 9169-5156 et al. (1 more author) (2020) Phosphoranyl Radical Fragmentation Reactions Driven by Photoredox Catalysis. ACS Catalysis. pp. 7250-7261. ISSN 2155-5435 https://doi.org/10.1021/acscatal.0c01923 Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. pubs.acs.org/acscatalysis Perspective Phosphoranyl Radical Fragmentation Reactions Driven by Photoredox Catalysis James A. Rossi-Ashton,* Aimee K. Clarke, William P. Unsworth, and Richard J. K. Taylor Cite This: ACS Catal. 2020, 10, 7250−7261 Read Online ACCESS Metrics & More Article Recommendations ABSTRACT: Photocatalytic generation of phosphoranyl radicals is fast emerging as an essential method for the generation of diverse and valuable radicals, typically via deoxygenation or desulfurization processes.
    [Show full text]
  • Radical-Induced Dephosphorylation of Fructose Phosphates in Aqueous Solution+
    Radical-Induced Dephosphorylation of Fructose Phosphates in Aqueous Solution+ Henryk Zegota++ and Clemens von Sonntag* Max-Planck-Institut für Strahlenchemie, Stiftstr. 34-36, D-4330 Mülheim 1 Z. Naturforsch. 36b, 1331-1337 (1981); received May 29, 1981 D-Fructo8e-l-phosphate, D-Fructose-6-phosphate, y-Irradiation, Radical Reactions, Mass Spectrometry Oxygen free N20-saturated aqueous solutions of D-fructose-1-phosphate and D- fructose-6-phosphate were y-irradiated. Inorganic phosphate and phosphate free sugars (containing four to six carbon atoms) were identified and their G-values measured. D-Fructose-1-phosphate yields (G-values in parentheses) inorganic phosphate (1.6), hexos-2-ulose (0.12), 6-deoxy-2,5-hexodiulose (0.16), tetrulose (0.05) and 3-deoxytetrulose (0.15). D-Fructose-6-phosphate yields inorganic phosphate (1.7), hexos-5-ulose (0.1), 6-deoxy-2,5-hexodiulose (0.36), 3-deoxy-2,5-hexodiulose and 2-deoxyhexos-5-ulose (together 0.18). On treatment with alkaline phosphatase further deoxy sugars were re- cognized and in fructose-1-phosphate G(6-deoxy-2,5-hexodiulose) was increased to a G-value of 0.4. Dephosphorylation is considered to occur mainly after OH attack at C-5 and C-l in fructose-1-phosphate and at C-5 and C-6 in fructose-6-phosphate. Reaction mechanisms are discussed. Introduction react with the solute molecules by abstracting The radiation chemistry of sugar phosphates in carbon-bound hydrogen atoms. Because of the high aqueous solutions has found already considerable reactivity of the OH radicals hydrogen abstraction attention [1-10].
    [Show full text]
  • An Invigorating Approach to Free-Radical Reactions
    Available online at www.sciencedirect.com ScienceDirect Biocatalytic hydrogen atom transfer: an invigorating approach to free-radical reactions Yuji Nakano, Kyle F Biegasiewicz and Todd K Hyster Initiating and terminating free-radical reactionis via hydrogen overcome these obstacles we propose searching beyond atom transfer (HAT) is an attractive means of avoiding substrate small molecule catalysts and reagents. prefunctionalization. Small molecule catalysts and reagents, however, struggle to execute this fundamental step with useful Biocatalysis offers an approach for overcoming the afore- levels of diastereoselectivity and enantioselectivity. In contrast, mentioned barriers. Many of nature’s transformations, nature often carries out HAT with exquisite levels of selectivity such as anaerobic metabolism [5] and DNA repair [6], for even electronically unactivated carbon–hydrogen bonds. By are understood to proceed by radical mechanisms. Addi- understanding how enzymes exploit and control this tionally, metal-cofactor dependent enzymes (such as fundamental step, new strategies can be developed to address P450s and non-heme iron/a-ketoglutarate-dependent several long-standing challenges in free-radical reactions. This enzymes) that catalyze highly selective C–H functiona- review will cover recent discoveries in biocatalysis that exploit a lizations (such as hydroxylation, amination or halogena- HAT mechanism to either initiate or terminate novel one- tion) are known to initiate by the abstraction of a hydro- electron reactions. gen atom from substrate [7]. Enzymes are also capable of differentiating prochiral intermediates with exclusive Address selectivity [8], making them suitable catalysts for the Department of Chemistry, Princeton University, Princeton, NJ 08544, stereoselective delivery of hydrogen atoms to radicals. USA Developing biocatalytic protocols that draw inspiration Corresponding author: Hyster, Todd K ([email protected]) from nature promises to afford general solutions to these fundamental problems.
    [Show full text]
  • This Student Paper Was Written As an Assignment in the Graduate Course
    77:222 Spring 2005 Free Radicals in Biology and Medicine Page 0 This student paper was written as an assignment in the graduate course Free Radicals in Biology and Medicine (77:222, Spring 2005) offered by the Free Radical and Radiation Biology Program B-180 Med Labs The University of Iowa Iowa City, IA 52242-1181 Spring 2005 Term Instructors: GARRY R. BUETTNER, Ph.D. LARRY W. OBERLEY, Ph.D. with guest lectures from: Drs. Freya Q . Schafer, Douglas R. Spitz, and Frederick E. Domann The Fine Print: Because this is a paper written by a beginning student as an assignment, there are no guarantees that everything is absolutely correct and accurate. In view of the possibility of human error or changes in our knowledge due to continued research, neither the author nor The University of Iowa nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they are not responsible for any errors or omissions or for the results obtained from the use of such information. Readers are encouraged to confirm the information contained herein with other sources. All material contained in this paper is copyright of the author, or the owner of the source that the material was taken from. This work is not intended as a threat to the ownership of said copyrights. K.M. Owens Tocopheroxyl Radical 1 Tocopheroxyl Radical by KJERSTIN M. OWENS Department of Free Radical and Radiation Biology The University of Iowa Iowa City, IA 52242-1181 For 77:222, Spring 2005 9.
    [Show full text]
  • Recent Advances of Stable Blatter Radicals: Synthesis, Properties and Applications Cite This: Mater
    MATERIALS CHEMISTRY FRONTIERS View Article Online REVIEW View Journal | View Issue Recent advances of stable Blatter radicals: synthesis, properties and applications Cite this: Mater. Chem. Front., 2020, 4,3433 Yu Ji, Lanxin Long and Yonghao Zheng * Radicals, organic molecules with unpaired electrons, are applied across different scientific disciplines such as electronics, energy storage and biochemistry. Among them, due to the extensive delocalization Received 29th February 2020, of the spin on the arene and the endocyclic nitrogens, Blatter radicals possess unique electronic and Accepted 15th June 2020 magnetic properties. Importantly, the excellence of chemical and thermal stability makes them have DOI: 10.1039/d0qm00122h great potential in applications. In this review, the synthesis, properties and applications of Blatter radicals from recent developments are summarized. Furthermore, the future developments of Blatter radicals are rsc.li/frontiers-materials also speculated. 1. Introduction The 1,2,4-benzotriazin-4-yl radical, also known as the Blatter radical, was first reported in 1968.1 Blatter-type radicals 1 have many interesting physical properties such as antiferromagnetism2–7 or ferromagnetic interactions,2,7–10 spin-p-delocalization,11 nar- row electrochemical window12,13 and low excitation energy,14,15 which allow them to attract more and more attention from Fig. 1 (a) The structure and (b) spin density distribution of Blatter radicals. scientists. More importantly, Blatter radicals have excellent stability to air and water, and are stable for up to 30 years.16 Hence, Blatter radicals have been applied in controllable the solid state, leading to a change in the magnetic Published on 17 June 2020.
    [Show full text]
  • Radicals in Natural Product Synthesis
    Chemical Society Reviews Radicals in natural product synthesis Journal: Chemical Society Reviews Manuscript ID CS-REV-05-2018-000379.R1 Article Type: Tutorial Review Date Submitted by the Author: 17-Jul-2018 Complete List of Authors: Romero, Kevin; University of Michigan, Department of Chemistry Galliher, Matthew; University of Michigan, Department of Chemistry Pratt, Derek; University of Ottawa, Department of Chemistry Stephenson, Corey; University of Michigan, Department of Chemistry Page 1 of 16 PleaseChemical do not Society adjust Reviews margins Journal Name Tutorial Review Radicals in natural product synthesis Kevin J. Romero,†a Matthew S. Galliher,†a Derek A. Pratt*b and Corey R. J. Stephenson*a Received 00th January 20xx, Free radical intermediates have intrigued chemists since their discovery, and an evermore widespread appreciation for their Accepted 00th January 20xx unique reactivity has resulted in the employment of these species throughout the field of chemical synthesis. This is most DOI: 10.1039/x0xx00000x evident from the increasing number of intermolecular radical reactions that feature in complex molecule syntheses. This tutorial review will discuss the diverse methods utilized for radical generation and reactivity to form critical bonds in natural www.rsc.org/ product total synthesis. In particular, stabilized (e.g. benzyl) and persistent (e.g. TEMPO) radicals will be the primary focus. Key learning points 1) This review will introduce the field of radical chemistry for organic synthesis to inspire further reading. 2) This review will distinguish between persistent and stabilized radicals and will relate the persistent radical effect. 3) The stereoelectronic factors that determine radical stability will be discussed. 4) Examples of radical reactions for natural product synthesis will be presented with an emphasis on the proposed mechanism for the radical transformation.
    [Show full text]
  • Radicals and the Birth and Death of DNA
    CHEMICAL BIOLOGY / BIOLOGICAL CHEMISTRY 275 CHIMIA 2001,55, No.4 Chimia 55 (2001) 275-280 © Schweizerische Chemische Gesellschaft ISSN 0009-4293 Radicals and the Birth and Death of DNA Bernd Giese Abstract: Radicals have important functions in the enzymatic synthesis of deoxyribonucleotides and their destruction by antibiotics. The chemical basis for these reactions is that radicals dramatically speed up ionic reactions. Nature has developed methods to generate these radicals under mild conditions in water as solvent. The 'catalytic' effect of these reactive intermediates is described. Keywords: Bleomycin' DNA· Enzymes· Radicals· Ribonucleotide reductase 1. Introduction ics like bleomycin or OHo radicals The chemistry of these radicals was (formed during oxidative stress) cause studied in order to understand the action Radicals play an important role in biolog- the death of DNA [1]. One of the inter- of the enzyme ribonucleotide reductase ical systems [1]. Among the targets for mediates involved in these reactions is and of the antibiotic bleomycin. radical attack are nucleotides as well as the 4'-DNA radical 5, which leads to their polymers, DNA and RNA. This at- strand cleavage even in the absence of tack leads to reactive intermediates with 3. Enzymatic Synthesis of radical centers at the carbohydrates or the °2' Deoxyribose heterocyclic bases of the nucleic acids. We have studied these radicals by syn- 2. Generation of the Radicals It is known, especially from the ex- thesis of their precursors and selecti ve periments of J. Stubbe and W.A. van der generation of the reactive intermediates. We have synthesized acyl selenide 11 Donck [4], that the first step of the enzy- Of special interest are the 3'- and 4'-nu- and pivaloyl ketone 16 as precursors for matic deoxygenation of ribonucleotides cleotide radicals because they are in- the 3'-and 4'-nucleotide radicals, respec- is the homolytic cleavage of their 3'-C,H- volved in the birth and the death of DNA.
    [Show full text]
  • An Overview on Disulfide-Catalyzed and -Cocatalyzed Photoreactions
    An overview on disulfide-catalyzed and -cocatalyzed photoreactions Yeersen Patehebieke Review Open Access Address: Beilstein J. Org. Chem. 2020, 16, 1418–1435. School of Chemistry and Chemical Engineering, Nanjing University, doi:10.3762/bjoc.16.118 Nanjing, 210023, China Received: 15 April 2020 Email: Accepted: 12 June 2020 Yeersen Patehebieke - [email protected] Published: 23 June 2020 This article is part of the thematic issue "Advances in photoredox Keywords: catalysis". cycloaddition; disulfide catalyst; isomerization; oxidation; photocatalysis; thiyl radical Guest Editor: T. Noël © 2020 Patehebieke; licensee Beilstein-Institut. License and terms: see end of document. Abstract Disulfides are versatile catalysts. They can be photocatalysts, hydrogen atom transfer (HAT) catalysts, cocatalysts, or initiators in photocatalytic reactions. Under photoirradiation, organic disulfides can be easily cleaved into free thiyl radicals (RS•) and can re- versibly add to unsaturated multiple bonds to catalyze a variety of functionalization reactions under mild conditions. In photoredox catalysis reactions, an excellent electron transfer ability and excellent radical properties also made these thiyl radicals powerful HAT catalysts. They have increasingly been proven useful in various types of organic photoreactions, such as cyclizations, anti- Markovnikov additions, aromatic olefin carbonylations, isomerizations, etc. They are a class of green, economic, mild, and chemo- selective radical catalysts that deserve more attention. The present review highlights the recent progress in the field of disulfide-cat- alyzed and -cocatalyzed photocatalytic reactions for different reaction types. Introduction Organic disulfides are often used as the skeleton for drugs, ability to reversibly add to unsaturated bonds, promoting a pesticides, rubber auxiliaries, polymers, and electronic materi- variety of reactions, renders them a class of green, economic, als [1].
    [Show full text]
  • Reactions of Radicals with Nucleophiles: the Nature of the Aryl Radical Intermediate in the Aromatic SRN1 Reaction James Michael Tanko Iowa State University
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1985 Reactions of radicals with nucleophiles: the nature of the aryl radical intermediate in the aromatic SRN1 reaction James Michael Tanko Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Tanko, James Michael, "Reactions of radicals with nucleophiles: the nature of the aryl radical intermediate in the aromatic SRN1 reaction " (1985). Retrospective Theses and Dissertations. 12112. https://lib.dr.iastate.edu/rtd/12112 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS This reproduction was made from a copy of a document sent to us for microfilming. While the most advanced technology has been used to photograph and reproduce this document, the quality of the reproduction is heavily dependent upon the quality of the material submitted. The following explanation of techniques is provided to help clarify markings or notations which may appear on this reproduction. 1.The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting through an image and duplicating adjacent pages to assure complete continuity.
    [Show full text]
  • DNA Radicals
    The chemistry of single-stranded 4’-DNA radicals: influence of the radical precursor on anaerobic and aerobic strand cleavage Bernd Giese*, Xenia Beyrich-Graf, Peter Erdmann, Mario Petretta and Urs Schwitter Department of Chemistry, University of Basel, St. Johanns Ring 19, CH-4056 Basel, Switzerland Background: Deoxyribosylnucleotide radicals with a these peroxides are formed either before or after the cleavage radical center at the 4’-position are important intermediates of the single-stranded DNA radical. Reactions in the pres- in radical-induced DNA strand cleavage. In the presence of ence of IsO, and/or HZ’*0 as well as subsequent transform- 0,, these DNA radicals yield cleavage products that are ations to the oxidized cleavage products confirmed the partly oxidized. In the past, the postulated peroxide interme- structure of the DNA peroxides. diates could not be detected directly because they were Conclusions: Our technique of selective DNA radical gen- unstable under the conditions of either radical generation, eration under mild conditions makes it possible to detect the work-up procedure, or the analytical techniques used. We labile reaction products of single-stranded DNA radicals and set out to generate and analyze these crucial intermediates in to gain further insight into their cleavage reactions. In cases radical-induced DNA strand cleavage under mild conditions. where a radical pair is formed, the shielding effect protects Results: Photolysis experiments with modified single- the DNA radical from external attack so that cleavage of the stranded oligonucleotides generated 4’-DNA radicals that single strand competes successfnlly with trapping by 02.This were trapped by 0,.
    [Show full text]