Selenium, the Element of Moon in Life on · PDF fileSelenium, the Element of Moon in Life on Earth ... 77Se is NMR active Se ... High blood levels of selenium

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