Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium

221 Pages·2013·7.742 MB·English

by  Craig A. Bayse, Julia L. Brumaghim

Biochalcogen Chemistry:
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In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
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In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
1152
ACS SYMPOSIUM SERIES
Biochalcogen Chemistry:
The Biological Chemistry of
Sulfur, Selenium, and
Tellurium
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3- Craig A. Bayse, Editor
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AmericanChemicalSociety,Washington,DC
DistributedinprintbyOxfordUniversityPress
In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
LibraryofCongressCataloging-in-PublicationData
Biochalcogenchemistry:thebiologicalchemistryofsulfur,selenium,andtellurium/
CraigA.Bayse,editor,OldDominionUniversity,Norfolk,Virginia,JuliaL.Brumaghim,
editor,ClemsonUniversity,Clemson,SouthCarolina;sponsoredbytheACSDivision
ofInorganicChemistry,Inc.,SocietyofBiologicalInorganicChemistry.
pagescm.-- (ACSsymposiumseries;1152)
1
00 Includesbibliographicalreferencesandindex.
w
52.f 1I.SBCNha9lc7o8g-e0n-8s-4-1C2o-n2g9r0e3s-s7es(.a2lk..Spauplfeurr)--Congresses.3. Selenium--Congresses.
1
1 4. Tellurium--Congresses. I.Bayse,CraigA.,editorofcompilation.
3-
1 II.Brumaghim,JuliaL.,editorofcompilation.III.AmericanChemicalSociety.Division
0
k-2 ofInorganicChemistry,sponsoringbody.IV.SocietyofBiologicalInorganicChemistry,
1/b sponsoringbody.
02 TP245.O9B562013
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In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
Foreword
The ACS Symposium Series was first published in 1974 to provide a
mechanism for publishing symposia quickly in book form. The purpose of
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In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
Preface
Theredoxactivityoftheheavierchalcogens, sulfur, seleniumandtellurium,
haslongbeenafocusofbiologicalandmedicalinterest. Thiolsandselenoproteins,
inparticular,playacriticalroleinmaintaininghealthystatesbyscavengingexcess
oxidants that contribute to increased risk of cancer, cardiovascular disease and
01 other oxidative-stress-related illnesses. To this end, natural sulfur and selenium
0
pr compounds found in many foods and a number of small synthetic organosulfur,
2.
15 -seleniumand-telluriumcompoundshavebeenexploredfortheirpotentialroleas
1
3- chemopreventives. Sulfur, especially in the form of cysteine, is a biomarker for
1
20 oxidativestressaswellasaligandintheactivesiteofnumerousmetalloproteins,
k-
b notably iron hydrogenase and transcription factors, where the conversion of
1/
02 thiolatestodisulfidesisanimportantredoxswitch. Thus, whilethechemistryof
1
0. ubiquitousoxygenisdistinctandoftenstudiedseparately,muchofthebiological
1
oi: chemistry of the heavier chalcogens are defined by their interaction with this
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3 | lightestmemberofthegroup. Highlightingboththepotentialvalueandthepitfalls
1
0 ofchalcogensinbiologyandmedicine,theNationalInstitutesofHealthhasspent
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5, over$250,000,000inthepastdecadeonselenium-supplementationclinicaltrials
ber alone,leadingtomixedresultsanddemonstratingtheclearneedforfurtherbasic
m
ce research.
e
D Thisbookhighlightsthebiologicalusesofheavychalcogensasakeyareaof
eb): focusinbioinorganicchemistryandaunifyingthemeforresearchinawidevariety
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e ( ofdisciplines. Recentachievementsinthesemultidisciplinaryeffortsarepresented
at that discuss the subtle, yet important roles of biochalcogens in living systems as
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n sulfur- and selenium-containing metabolic intermediates and products (Chapters
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ati 1 and 10) and in their oxidation when coordinated to metals (Chapters 3 and 4).
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their functionalities are also discussed (Chapters 2 and 6), as are new directions
in biochalcogen applications to redox scavenging, both in terms of synthesis
(Chapters 7 and 8) and mechanistic modeling (Chapter 9). Tellurium, with no
natural biological function, is represented together with sulfur and selenium as
a phasing agent in nucleic acid crystallography and for other biological studies
(Chapter5).
Thisbookwillserveasausefulcollectionofreviewsandresearchresultsinthis
diversefield,encompassingresearchinbioinorganicchemistry,organicsynthesis,
computational approaches, and biochemistry; as an inspiration for researchers
wishing to enter the variety of fields that encompass these multidisciplinary
research efforts; and as a useful resource for undergraduate or graduate courses
focusingonmaingroupandtransitionelementbiochemistry. Wehopethatawide
audiencefindsthisbookahelpfulresourceforthisrapidlyexpandingfield.
ix
In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
WethanktheAmericanChemicalSociety’sDivisionofInorganicChemistry
and the Society for Biological Inorganic Chemistry for their generous support of
the ‘Biochalcogen Chemistry’ symposium at the 2012 National ACS Meeting in
Philadelphia.
CraigA.Bayse
DepartmentofChemistryandBiochemistry
OldDominionUniversity
HamptonBoulevard
Norfolk,Virginia23529,U.S.A.
[email protected](e-mail)
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01 ChemistryDepartment
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1/ Clemson,SouthCarolina29634-0973,U.S.A.
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In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
©2013AmericanChemicalSociety
odorantsbyORs.
first time the role of copper in detection of sulfur-containing
discriminate MTMT. The above work establishes for the
assay showed that mice injected with TEPA failed to
responseofMOR244-3toMTMT.Anolfactorydiscrimination
compoundstested. UseofaCu-chelator(TEPA)abolishesthe
odorants, such as odorous trans-cyclooctene, among >125
MTMT,relatedsulfurcompounds,andothermetal-coordinating
is required for activation of MOR244-3 toward ppb levels of
previouslyproposedbutunproven. RecentworkshowsthatCu
1 Metal ion involvement in interaction of thiols with ORs was
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1 (methylthio)methanethiol (MTMT) in heterologous cells.
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d Olfactory receptors (ORs), located in olfactory sensory
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Eric Block and Hanyi Zhuang
*,1 2,3
Olfactory Receptor that Requires Copper
Smelling Sulfur: Discovery of a Sulfur-Sensing
Chapter 1
In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
2
proteindegradationproductsfoundinputridfood,andH2Sispresentinoxygen-
etc.) specieswhousethemastrailmarkers(12). MalodorousVSCsandaminesare
gas odorants, are found derivatized in anal scent glands of musteloid (weasels,
Strong-smelling heterocyclic thioethers, thietane and thiolane, also used as
AmericanChemicalSociety.
Figure2. Cysteine-S-conjugateoriginofbellpepperVSCs(10). Copyright2011,
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as in scent markers, e.g., Chevron’s Scentinel® (11), for detection of otherwise
(Figure 1) (9) and bell peppers (Figure 2) (10), among other sources, as well
skunky-smelling beer (7), male mouse urine (8), and in the aromas of durian
withverylowodorthresholdsarealsopresentingrapefruit(5), skunkscent(6),
perceived at levels as low as 0.001 ng/L (~0.001 parts per trillion) (4). Thiols
3-methyl-3-sulfanylhexan-1-ol, present in onions and in armpit odor (3) can be
monkeys are yet more sensitive, detecting 0.001 ppb ethanethiol (2), and chiral
billion (ppb) are “clearly perceptible to the sense of smell” (1). Spider
Fischer wrote that concentrations of ethanethiol as low as 0.05 parts per
smell toward low-valent, volatile sulfur compounds (VSCs). In 1887, Emil
Humans, and other animals, have an exquisitely sensitive sense of
Introduction
In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.
3
centre would be stabilized by coordination, perhaps to a protein thiolato-group,
mostlikelycandidateforametallo-receptorsiteinolfaction,”andthat“theCu(I)
receptor. . . containing a transition metal at the active site,” that Cu(I) is “the
sulfides and other strong-smelling small molecules “bind chemically to a nasal
of taste involved copper. In 1978, Crabtree (23) proposed that H2S, thiols and
thiolsandamines. In1969,HenkinandBradley(22)suggestedthatthephysiology
(generallyintheformofmetalloproteins)maymediatetasteorodorperceptionof
researchershaveproposedthattransitionmetalssuchasZn2+,Ni2+,Cu2+,orCu+
Latin mercurium captans (“capturing mercury”). Over the past 40 years several
about the possible role of metals in olfaction: “mercaptan” comes from the
The alternative name for ethanethiol, ethyl mercaptan, provides a clue
Possible Role of Metals in Olfaction
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blic to understand the molecular basis for sensitive olfactory detection of VSCs,
Pu hundredmilliontimesmoredelicate”(18). Thischapterdescribesrecentefforts

ethyl mercaptan is perceptible at 0.3×10-8 % wt./wt.; our perception of it is one
ethanol “is only perceptible in air in a concentration of 0.4 % wt./wt., whilst
structurally similar molecules ethanol and ethanethiol (Figure 3). For example,
sense of smell, and why there is such a striking difference in smell between the
Little is known about perception of low molecular weight VSCs by the
asskunky(16, 17).
tracelevelsisperceivedasfruity,whereasinhigherconcentrationsitisdescribed
of 3-methyl-2-butene-1-thiol in beer (7), and dimethyl sulfide in wine, which at
perceivedasfavorableandhigherconcentrationsasunpleasant,e.g.,asinthecase
perceptionofVSCscanvarywithconcentration,withlowerconcentrationsbeing
compounds to avoid intoxication (12–15). It should be noted that the sensory
depleted air, hence the need for animals to have heightened sensitivity to these
In Biochalcogen Chemistry: The Biological Chemistry of Sulfur, Selenium, and Tellurium; Bayse, C., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 2013.