Free Radical Nomenclature, Suggestions

Home , Hydron (chemistry), Hydroperoxyl, Hypobromous acid, Hypochlorous acid, Hypoiodous acid, Nitroxyl

FRRB Free Radical Nomenclature Page 1 of 8

Garry R. Buettner, Ph.D. Free Radical and Radiation Biology Program Med Labs B180K The University of Iowa Iowa City, IA 52242-1181 2018.01.17

The purpose of this document is to provide an easy reference to some of the language of Redox Radical Biology. We provide here a beginning guideline to nomenclature and notation for free radicals and related redox species. The International Union of Pure and Applied Chemistry (IUPAC) does not provide suggestions on all abbreviations we might use; attached are the suggestions of the FRRB Program at The University of Iowa. Guidelines for nomenclature in Free Radical Biology can be found in [1, 2, 3, 4, 5 and references therein].

I. Free Radical and Oxidant Notation and Nomenclature

In chemical formulae, as well as when using abbreviations, a free radical is denoted by a superscript dot to the right preceding any charge. This placement of the dot will not interfere with indication of mass number, atomic number, or composition.

– – H O2 CO2 HO H3C NO 2 O2 would be the radical notation for ground state dioxygen, O2.

Table 1. Formulae and IUPAC Recommended Names of Simple Compounds Containing C, H, N, and O in Free Radical Biology Species Common Systematic Name Alternative and Name Comments

CO carbon monoxide carbon monoxide oxidomethanediyl

CO2 carbon dioxide carbon dioxide dioxidomethane carbon dioxide CO – dioxidocarbonate (•1–) oxidooxomethyl radical 2 radical anion •– CO3 carbonate radical trioxidocarbonate(•1–)

H hydrogen atom monohydrogen(•)

H+ proton hydron, monohydrogen(1+) not to be confused with H•

H2O water dihydrogen monoxide oxidane

H2O2 hydrogen peroxide dihydridodioxide dioxidane H3C methyl radical HNO nitroxyl nitrosyl hydride

HNO2 nitrous acid

HNO3 nitric acid

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HO hydroxyl radical hydridooxygen(•) oxidanyl

dioxidanide, – hydrogendioxide(1-); HO hydridodioxygen (1-) 2 hydrogenperoxide(1-); hydroperoxide is not recommended

hydroperoxyl, but is dioxidonyl, hydrodioxyl, perhydroxyl hydridodioxygen(•) HO2 obsolete does not make sense hydrogen trioxide HO • hydridotrioxygen(•) trioxidanyl 3 radical HOCO• hydroxidooxidocarbon(•) Protonated carbon dioxide radical

• HOCO 2 hydroxidodioxidocarbon(•) Protonated carbonate radical

HOCO• hydroxidooxidocarbon(•)

• HOCO 2 hydroxidodioxidocarbon(•)

HOCl hypochlorous acid hydrogenoxidochlorate

HOBr hypobromous acid hydrogenoxidobromate

HOI hypoiodous acid hydrogenoxidoiodate hypothiocyanous HOSCN hydrogenoxidothiocyanate acid nitroxyl, protonated - HNO See [6] for chemistry and NO form of NO- HON2• hydroxidonitrogen(2•)(triplet) hydrogen oxidonitrate(2•)(triplet) HOOCO• (hydridodioxido)oxidocarbon(•) HOONO peroxynitrous acid hydrogenoxidoperoxidonitrate nitrosodioxidane

H2S hydrogen sulfide dihydrogen sulfide

HSNO thionitrous acid

•– (NO)2 bis(oxidonitrate)(N – N)(•1-)

N2O nitrous oxide dinitrogen monoxide

•– N2O oxidodinitrate(•1-)

N2O3 dinitrogen trioxide

N3 azidyl radical trinitrogen(2N – N)(•) nitric oxide, but is oxidonitrogen(•) oxoazanyl, nitrogen monoxide NO obsolete

NO+ nitrosonium ion

NO- nitroxyl anion conjugate base of HNO

NO(2•)– Nitroxy ?? oxidonitrate(2•1–) (triplet)

– NO2 nitrite dioxidonitrate(1–) NO2 nitrogen dioxide dioxidonitrogen(•)

•2– NO2 dioxidonitrate(•2-)

– NO3 nitrate trioxidonitrate(-) NO3 nitrogen trioxide trioxidonitrogen(•) nitrosoxidanyl

•2– NO3 trioxidonitrate(•2-)

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• O– radical anion of HO oxide(•1-) oxidanidyl

– O2 superoxide dioxide(•1-) dioxidanidyl

•+ O2 dioxygen(•1+)

2 oxygen, usually O2 dioxygen (triplet) dioxidanediyl written as O2

O3 ozone trioxygen

– O3 ozonide trioxide(•1-) trioxidanidyl

OCl– hypochlorite oxidochlorate(1-)

OBr– hypobromite oxidobromate(1-) OI– hypoiodite oxidoiodate(1-) OSCN– hypothiocyanate oxidothiocyanate(1-) OCOO– or – carbonate radical (dioxido)oxidocarbonate(•1–) CO3 ONOO– peroxynitrite oxidoperoxidonitrate(1-) nitrosodioxidanide

ONOOH peroxynitrous acid hydrogen-oxidoperoxinitrate nitrosodioxidane

ONOO (dioxido)oxidonitrogen(•) nitrosodioxidanyl

II. Free Radical Nomenclature You Need to Know

Table 2 Common Abbreviations Species/Abbreviation* Name ascorbate, general; ascorbic acid; ascorbate monoanion; ascorbate radical

OH OH OH O HO O O HO O pK1 = 4.1 O pK2 = 11.8 HO O

HO OH O OH O O AscH - 2- – – 2 AscH Asc Asc; AscH2, AscH ; Asc

OH OH O O HO O HO O + R + RH O OH O O AscH Asc

CAT catalase Desferalâ trade name for deferrioxamine mesylate

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H O O H N C NH C NH (CH2)5 (CH2)2 (CH ) (CH2) 2 5 (CH2)5 CH3 N C N C N C HO O HO O HO O

Deferrioxamine (Desferal)

5,5-dimethyl-pyrroline-1-oxide, a spin trap

H + R N DMPO N R O O DMPO Nitroxide Radical (Nitrone Spin Trap) (Aminoxyl Spin Adduct)

diethylenetriaminepentaacetic acid (Shown is the completely ionized species.) O O

DTPA or DETAPAC O C H2C CH2 C O N (CH2)2 N (CH2)2 N O C H2C CH2 C O CH2 C O O O O EDRF endothelium-derived relaxing factor

ethylenediaminetetraacetic acid (Shown is the completely ionized species.) O O EDTA O C H2C CH2 C O N CH2 CH2 N O C H2C CH2 C O

O O EPR electron paramagnetic resonance ESR electron spin resonance, identical with EPR G gauss GPx glutathione peroxidase glutathione disulfide reductase; often referred to as glutathione GR reductase (a misnomer) Grx glutaredoxin GS• glutathiyl radical or glutathionyl radical

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O NH3 O H O O C CH CH2 CH2 C NH C C NH CH2 C O O CH2

S Glutathione; not reduced glutathione, a misnomer

O NH3 O H O O C CH CH2 CH2 C NH C C NH CH2 C O O GSH CH2 SH

glutamate cysteine glycine

GSSG glutathione disulfide; not oxidized glutathione, a misnomer 2GSH à GSSG + 2e- + H+ GST glutathione S transferase H+ proton, hydron; not to be confused with H• LDL low density lipoprotein MDA Malondialdehyde O O O OH

NBT nitroblue tetrazolium

H3CO OCH3 N N N N N N N N

O N NO 2 2

NOS nitric oxide synthase 1 O2 singlet oxygen OH– hydroxide anion, not to be confused with HO• PBN a-phenyl-N-tert-butyl nitrone, a spin trap

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O CH3

CH N C CH3 CH 3 Prxd often Prx peroxiredoxin PhGPx phospholipid hydroperoxide glutathione peroxidase (GPx-4) POBN a-[4-pyridyl 1-oxide]-N-tert-butyl nitrone, a spin trap O CH3

O N CH N C CH3 CH 3 PUFA polyunsaturated fatty acid, for example

14 11 8 5 OH H11C5 (CH2)3 C O arachidonic acid RNS reactive nitrogen species RO alkoxyl radical; not alkoxy ROO• alkyl dioxygen(•), alkyldioxyl, alkylperoxyl radical; not peroxy ROOH alkyl hydroperoxide ROS reactive oxygen species R-SH thiol R-S- thiolate anion- R-SOH sulfenic acid

R-SO2H sulfinic acid

R-SO3H sulfonic acid SOD superoxide dismutase CuZnSOD copper,zinc-superoxide dismutase (SOD-1) MnSOD manganese-superoxide dismutase (SOD-2) FeSOD iron-superoxide dismutase ECSOD extracellular superoxide dismutase (SOD-3) TBARS thiobarbituric acid reactive substances Trx thioredoxin * These are commonly used abbreviations. Others appear in the literature.

Buettner GR Page 6 FRRB Free Radical Nomenclature Page 7 of 8 III. Enzyme Reactions You Must Know to Understand Free Radical Biology

A. The reaction for superoxide dismutase (SOD) is:

SOD – – + O2 + O2 + 2 H ¾¾¾® O2 + H2O2

B. The reactions for catalase (CAT) are:

CAT

2 H2O2 ¾¾¾® O2 + 2 H2O Catalytic Rxn

CAT

H2O2 + DH2 ¾¾¾® D + 2 H2O Peroxidatic Rxn

C. The reaction for glutathione peroxidase (GPx) is:

GPx ROOH + 2 GSH ¾¾¾® ROH + H2O + GSSG

where R = H is allowed.

D. An overview of the reaction of the peroxiredoxins is:

Prx H2O2 + Trx-(SH)2 ¾¾¾® 2 H2O + Trx(S-S)

E. Overview of Antioxidant network

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This overview is from [7]. End

IV. References

1 Koppenol WH. (2000) Names for inorganic radicals. Pure Appl Chem. 72:437-446. http://www.iupac.org/publications/pac/2000/7203/7203pdf/7203koppenol_437.pdf 2 Powell WH. (1993) Revised nomenclature for radicals, ions, radical ions and related species. Found at: http://www.chem.qmul.ac.uk/iupac/ions 3 Koppenol WH. (1990) What is in a name? Rules for radicals. Free Radic Biol. Med 9:225-227. http://dx.doi.org/10.1016/0891-5849(90)90032-E 4 Traynham JG. (1986) A short guide to nomenclature of radicals, radical ions, iron-oxygen complexes and polycyclic aromatic hydrocarbons. Adv Free Radic Bio Med. 2:191-209. http://dx.doi.org/10.1016/S8755-9668(86)80029-1 5 Koppenol WH. (2002) NO nomenclature? Nitric Oxide Biol Chem. 6:96-98. http://dx.doi.org/10.1006/niox.2001.0406 6 Fukuto JM, Switzer CH, Miranda KM, Wink DA. (2005) Nitroxyl (HNO): chemistry, biochemistry, and pharmacology. Annu Rev Pharmacol Toxicol. 45:335-55. PMID: 15822180 http://dx.doi.org/doi:10.1146/annurev.pharmtox.45.120403.095959 7 Ng CF, Schafer FQ, Buettner GR, Rodgers VGJ. (2007) The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical insight into in vivo H2O2 and GPx concentrations. Free Rad Res. 41:1201-1211. PMID: 17886026 http://dx.doi.org/10.1080/10715760701625075

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