Selenium, the Element of Moon in Life on Earth · Maximum doses: 400 μg per day. oxidative stress...
Transcript of Selenium, the Element of Moon in Life on Earth · Maximum doses: 400 μg per day. oxidative stress...
Selene: Greek Goddess of the Moon
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Selenium, the Element of Moon in Life on Earth
Selenium discovered by Swedish scientist J. J. Berzelius (1817)
Red deposit – remains after the roasting of copper pyrites during H2SO4
manufacturing
Named after Greek mythological Goddess (in Greek, Selene = Moon)
Natural Resources of Se and its stable Isotopes Abundance
Mass Natural
Abundance
74 0.88
76 8.95
77 7.65 (I = ½)
78 23.51
80 49.62
82 9.39
White J. R.; Cameron. A. E. Phys. Rev., 1948, 74, 991-1000.
Minerals containing selenium are very
uncommon
70th in abundance of the 88 that are present
naturally in the earth crust
Most selenium is recovered as a by-product
of processing copper ores (Copper Pyrites)
77Se is NMR active
Se
Atomic Mass – 79.9165
http://en.wikipedia.org/wiki/File:SeBlackRed.jpg
http://www.chemistryexplained.com/A-Ar/Allotropes.html
Grey (trigonal) selenium (Sen helical chain polymers)
Grey (rhombohedral) selenium (Se6 molecules)
Three deep-red (monoclinic) forms (α, β, and γ-selenium containing Se8 molecules)
Amorphous red selenium
Black vitreous selenium
Most thermodynamically stable and the densest form: gray (trigonal)
Allotropes of Selenium
Selenium chemistry
Group 16
O
S
Se
Te
Po
Large, soft atom, much softer than sulfur
Big, squashy atom; its electron clouds large, diffuse andeasily distorted
Nucleus exerts little effect on what happens at thePeriphery
Means Se can spread its electron over many neighbors
Dual nature; ability to donate electrons (metallic) andtake electrons (nonmetallic) metalloid
H2O 119
H2S 93
H2 Se 75
H2Te -
RS- 8.5
RSe- 5.2
~ Physiological pKa
pKaDissociation Energies (kcal/mol)
H2NOH
O
SeH
H2NOH
O
SH
Selenocysteine (Sec)Cysteine (Cys)
Ligands in catalysis
Se
Metal chalcogenides (CdSe) - Semiconductors
Importance of Selenium and its Derivatives
Materials Chemistry
Selenium Toxicity
Severely damaged hoofs
Selenium in Biology
Marco Polo (1254-1324) writes for Kublai Khan in his travelogue into China about poisonous plants that animals ate and shed their hooves
Selenosis
Blind Staggers
Alkali Disease
High blood levels of selenium (greater than 100 μg/dL) Symptoms - Gastrointestinal upsets, hair loss, white blotchy nails,
garlic breath odor, fatigue, irritability, and mild nerve damage
Acute selenium poisoning incows and sheep caused byingestion of plants with highselenium content
Acute selenium poisoning inCattle (Moxon, 1937)
Selenium deficiency (1930, China)
Keshan disease, which results in an enlarged and poor heartfunction
Hypothyroidism (worsens iodine deficiency)
Weakens immune system
Selenium Supplements
http://www.mineralifeonline.com/pd-selenium-8oz.cfm
• Serving Size : 2 Droppers (2 mL) daily in water or juice as maintenance
• Servings Per Container : 120
Boost Your Immune System with Selenium
Maximum doses: 400 μg per day
oxidative stress
O2 O2
O2 O2
H2O2
Fe2+
Fe3+
OH H2O
H
H2O
SOD
MPO
HOCl
H2O2 H2O
Cl
NO
ONOO
_
_
e
1O2 +_
O2
_
H2O2 OH
lactoferrin
SOD
peroxidationX
Fe2+Fe3+
GPx2H2O
H2O + O2
ONOO_
NO
oxidationnitration
nitrosationX
antioxidantenzymes
lipid
catalase
ROS Generating and Scavenging Systems
MPO - Myeloperoxidase
Damage of cell membranes
DNA cleavage
Guanine Oxidation
Neurodegenerative diseases like
Alzheimer, Parkinson’s
Ageing
Inflammation
Certain Cancers
Reactive Oxygen Species (ROS)
Cellular thiols (Glutathione, thioredoxine) – Redox Buffers
Antioxidants – Ascorbic acid– Vitamin E and other Phenolic compounds
Antioxidant enzymes
Catalase is a hemeprotein – Catalyzes the disproportion of H2O2
Superoxide dismutase: Cu-Zn-SOD, Fe-SOD, Mn-SOD– Catalyzes the disproportionation of HO2
Sulfiredoxine is a cysteine containing enzyme - Reduction of H2O2
Glutathione peroxidase is a selenocysteine containing enzyme - Reduction of H2O2
The defense system
Selenoenzymes (14 discovered)
Enzyme Reaction
Formatedehydrogenases
HCOOH → CO2 + 2H+ 2e-
Glysine reductase Gly + 2e- + 4H+ + ADP + Pi → Acetate+ NH4
+ + ATP
Glutathioneperoxidases (GPx)
H2O2 + 2GSH → 2H2O + GSSG
Phospholipide-hydroperoxide-GPx
ROOH + 2GSH → ROH + H2O + GSSG
Type-I iodothyroninedeiodinase
L-Thyroxine + 2e- + H+ → 3,5,3'-iodothyronine + I-
Thioredoxin reductase NADPH + Trxox → NADP+ Trxred
Selenophosphatesynthatase
HSe- + ATP → HSe-PO3H2 + AMP + Pi
Selenoprotein P Antioxidant?
GSH – Reduced glutathione
ROOH – Lipid hydroperoxide
Trx - Thioredoxin
Selenium Biochemistry Emerged in 1973, after the discovery twobacterial enzymes
The thyroid is one of the largest endocrine glands in the body
This gland is found in the neck inferior (below) to the thyroid cartilage (also known
as the Adam's apple in men) and at approximately the same level as the cricoid
cartilage
The thyroid controls how quickly the body uses energy, makes proteins, and controls
how sensitive the body should be to other hormones
T3T4
Ratio of T4/T3 released in blood = 20/1
Iodothyronine Deiodinase
T4 T3
Berry, M. J.; Banu, L.; Larsen, P. R. Nature 1991, 349, 438.
Thiol cofactor
Is not yet identified
Catalytic Cycle of Iodothironine Deiodinase
ESeH
ESeI
T4
T3RSH
RSSR+HI
Glutathione Peroxidase (GPx)
ROOH + 2GSH ROH + GSSG + H2OGPx
Cytosolic GPx (cGPx) – uses GSH as co-substrate
Reduction of hydrogen peroxides and organic peroxides
Tetramer of four identical subunits; each subunit contains a
selenocysteine residue
Catalytic triad – SeCys, Gln, Trp - Selenolate is highly stabilized
HN
NH
OH
O
O
SHO
COOH
H2N -Glu-Cys-Gly
(GSH)
Structure of Glutathione Peroxidase
Tetramer of four identical subunits; each subunit
(M.W. 21,000 Dalton)
contains a selenocysteine residue at the active site
Wendel et al. Eur. J. Biochem. 1983, 133, 51
Se
N
SeCys H2N
O
Trp148
.....
.....
+HH
Gln70
Synthetic Mimics
Wilson, S. R.; Zuker, P, A.; Huang, R. C.; Spector, A. J. Am. Chem. Soc. 1989, 111, 5936.
Rupinder, K.; Singh, H. B.; Patel. R. P. Dalton Trans. 1996, 2719.
Catalytic Activity
Time
Abs UV Method using Benzenethiol as GSH Alternative
Initial reduction rates of hydrogen peroxides
UV absorption increases at 305 nm due to the formation of PhSSPh
C = (1C0-2a)/( 1-22)
C = conc. of PhSH, C0 = Initial conc. of PhSH, a = absorption
1 = Molar extinction coefficient of PhSSPh = 1.24 X 103 M-1cm-1
2 = Molar extinction coefficient of PhSH = 9 M-1cm-1
Since 1 2, C = C0 - 2a/1
* Initial reduction rates 1/v vs 1/C plots - Lineweaver-Burk plots
* Comparison of v0 at PhSH 1 mM level
2
Catalytic Activity
Lineweaver-Burk plots obtained for 0.01 mM of 18. The initial H2O2 concentration
was fixed to 3.75 mM. The initial PhSH concentration (C0) was 1 mM
Best Fit : Y = 4.73111X + (-3.04687)
Initial Reduction Rate (v0) = 593.74 µm min-1. This v0 was obtained by
substituting X = 1 mM in the above linear equation.
1.0 1.2 1.4 1.6 1.8 2.0
0
4
8
[18] = 0.01 mM
1/[PhSH] (mM )-1
1/v
(m
M
m
in)
-1
Initial Reduction Rates (ν0) of H2O2 (3.75 mM) with PhSH (1 mM) in methanol in the presence of various selenium catalysts (0.01 mM)
Catalysts ν0 M min-1
0.55 (0.18)
3.39 (0.37)
3.16 (0.52)
3.83 (0.32)
5.78 (0.79)
28.38 (3.88)
Catalysts ν0 M min-1
36.10 (0.12)
574.01 (23.98)
466.49 (28.26)
Inactive Catalysts
[R, S; R, S] (+)
[S, R; S, R] (-)
GPx-Like Activity of Chiral Ferrocenyl Selenium Derivatives
Intermediates and Catalytic Cycle
Nucleophilic attack by thiol at
sulfur and not at selenium
Strong SeN interaction
Does not favor selenol formation
Thiol exchange occurs
Weak SeN interaction
Favors selenol formation
No thiol exchange
Intramolecular Interaction and Thiol Exchange
Mugesh, G.; Singh, H. B. Chem. Soc. Rev. 2000, 29, 347−357.
Mugesh, G.; Panda, A.; Singh, H. P.; Punekar, N. S.; Butcher, R. J. Chem. Commun. 1998, 2227−2228.
Mugesh, G.; Panda, A. Singh, H. B.; Punekar, N. S.; Butcher, R. J. J. Am. Chem. Soc. 2001, 123, 839−850.
Group
Group
Acknowledgements
o Prof. Ray J. Butcher
o Prof. N. S. Punekar
DST, CSIR, BRNS
Department of Chemistry
SAIF and IRCC
IIT Bombay
UGA - Codon
Uracil-Guanine-Adenine (UGA)
This codon is generally a stop codon
The UGA codon is made to encode selenocysteine by the
presence of a SECIS element (SelenoCysteine Insertion
Sequence) in the mRNA
Microreview . Thomas Wirth et al.
Recent Advances in Organoselenium Chemistry
Wirth et al., Eur. Org. Chem. 2009, 1639.
Application of Organoselenium Compounds in Organic Synthesis
CAS Number: 1666-13-3Commercial
Diphenyl Diselenide
Thiol exchange
In-Situ 77Se NMR Studies/Oxazoline Derivatives