Active oxygen

A 　 Review of Active Oxygen ; Basic concept and Applications to Industrial, Environmental, Pharmaceutical, and Medical Fields活性酸素の基礎と工業、環境、医療分野への応用

By Isamu Katsuyama

Topics ( トピックス）

A. Generation and Physiological Action of Active Oxygen Species in an Organism 生体内の活性酸素種の生成と生理作用

B. Practical Applications of Active Oxygen Species and Their Future　

活性酸素種の応用実例とその将来性C.

Physicochemical Aspects of Molecular Oxygen and Active Oxygen Species

酸素および活性酸素種の物理化学

A. Generation and Physiological Action of Active Oxygen Species in an Organism 生体内の活性酸素種の生成と生理作用

B. Practical Applications of Active Oxygen Species and Their Future　

活性酸素種の応用実例とその将来性C.

Physicochemical Aspects of Molecular Oxygen and Active Oxygen Species


D. Method for the Generation of Singlet Oxygen

一重項酸素の発生法E. Method for the Detection of Singlet Oxyge

n一重項酸素の検出・測定法

F. Example for Successful Application of Singlet Oxygen

一重項酸素の応用へ成功例

D. Method for the Generation of Singlet Oxygen

一重項酸素の発生法E. Method for the Detection of Singlet Oxyge

n一重項酸素の検出・測定法


一重項酸素の応用へ成功例

A. Generation and Physiological Action of Active Oxygen Species in an Organism生体内の活性酸素種の生成と生理作用

A. Generation and Physiological Action of Active Oxygen Species in an Organism生体内の活性酸素種の生成と生理作用

O2 O2-, H2O2, HO., 1O2 H2O

Active Oxygen SpeciesAntioxidant

Cyto-toxicity

Application for Biochemical Reactionsand Defense Systems against Other Organisms

e-

Food Generation of Energy

excess amount

Example of Application of Active Oxygen

Species for Biochemical Reactions活性酸素種の生化学反応の例

1. Biosynthesis of Prostaglandines (PGs)プロスタグランジン類の生合成

2. Biosynthesis of Thyroid Hormones甲状線ホルモンの生合成

1. Biosynthesis of Prostaglandines (PGs)プロスタグランジン類 (PGs) の生合成

COOH

OOH

O

O

COOH

COOH

OH

O

O

COOH

OH

O

HO

Arachidonic Acid

PGG2

prostaglandin syntase

O2

PGH2PGE2

2. Biosynthesis of Thyroid Hormones (T4)甲状線ホルモン (T4) の生合成

OH

I I

COO-

O-

O

I I

COO-O

O

H

HO

O

I I

O

COOR

O

I I

O

O-OC

O-OH

DHPPA 1 2 3

DHPPAO2

O2

O

I I

O

HOOC

O

O

I I

O

HOOC

O

OHO

COOHH2N

OH

II

I

I

Thyroxine (T4)

DIT DITT4

COOH

NH2

OH

II

DIT

4 5

H2O2

V. B. Oza et al., J. Am. Chem. Soc. 1997, 119, 11315.

Example of Application of Active Oxygen Species for Defense System against Other Organisms

活性酸素種の生体防御の例

1. Disinfection in the Mouth （口腔内殺菌）2. Disinfection in Leukocyto （白血球による殺

菌）

In summary, active oxygen species are necessarily generated in an organism, and have important roles in biochemical reactions and defense systems against other organisms.

In summary, active oxygen species are necessarily generated in an organism, and have important roles in biochemical reactions and defense systems against other organisms.

B. Practical Applications of Active Oxygen Species and Their Future 　

活性酸素種の応用例とその将来性

B. Practical Applications of Active Oxygen Species and Their Future 　

活性酸素種の応用例とその将来性

1. Application for Medical Treatment 　　　　　　　（病気治療への応用）

2. Development of New Functional Materials 　　 ( 新規機能性物質の開発）

3. Application for Environmental Purification 　　 ( 環境浄化への応用）

1. Application for Medical Treatment

A) Treatment of Cancer ( 癌治療）• Anticancer Drugs ( 抗癌剤）• Photodynamic Therapy, PDT 　

( 光力学療法）

B) Treatment of Bacterium Diseases ( 細菌病治療）

C) Treatment of Virus Diseases ( ウイルス病治療）

Anticancer Drug

• Some anticancer drugs can generate active oxygen species, mainly, the hydroxy radical, which is known to cause DNA strand breaks.

O

O

OH

OHMeO O

OH

X

O

sugar

Example

Anthracyclines

Characteristics of This Type of

Anticancer Drug (AD)

i. This type of AD has a high activity in the tissues because the hydroxy radical is the most toxic species.

ii. In general, AD tends to be retained not only in tumor tissues but also in normal tissues.

This type of AD often leads to a high toxicity in normal tissue.Improvement of the selectivity should be necessary.

Photodynamic Therapy, PDT 　

Abstract

i. PDT is a treatment modality using a photosensitising drug and light to kill cells.

ii. The clinical use of PDT requires the presence of a photosensitizing agent, oxygen, and light of a specific wavelength.

Mechanism of Tumor Destruction Using PDT

Photosensitizer

Activated Photosensitizer

1O2

Cytototoxic Oxyproducts

Cellular Destruction

Light

3O2

Substrate

1O2

3O2

The Appeal of PDT in Oncology

i. Singlet oxygen has both a short lifetime and a short radius of action.

ii. Photosentisitizer tends to be retained in tumor tissues for a longer period of time as compared with normal tissues.

These potentials can lead to minimal toxicity in normal tissue.

Clinical Applications of PDT

• PDT has been clinically tested in a variety of tumors including intra-peritoneal, gastrointestinal, genitourinary, pulmonary, head, neck and skin cancers.

Major Problems in PDT

i. Limited depth of tissue penetration and exited skin phototoxicity due to the limitation of older photosensitizers

ii. PDT has a limited application due to its mechanism.

Examples of Photosensitizers

First Generation of Photosensitizers

NH N

HNN

CO2H

OH

OH

HO2C

Haematoporphyrin and its derivatives

Second Generation of Photosensitizers

NH

N

N

N N

HNN

N

Phtalocyanine and its derivatives

Conclusion of PDT

• Development of newer photosensitizers is in progress in order to solve the problems.

• According to such improvement and the potential for minimal toxicity in normal tissue, PDT will become an important part of cancer treatment.

Future Directions of Cancer Treatment

• Although PDT has a limited application, it can be used with other therapies such as anticancer drug.

• Studies on combining PDT with the other therapeutic modalities are in their initial phases, and will improve outcome and minimize toxicity of cancer treatment.

• Although PDT has a limited application, it can be used with other therapies such as anticancer drug.

• Studies on combining PDT with the other therapeutic modalities are in their initial phases, and will improve outcome and minimize toxicity of cancer treatment.

2. Development of New Functional

Materials 　　

1O2

XR

H

OO

O O

O

HO

XR

A

B

CEn

[2+2]

[4+2]

Singlet oxygen is a useful reagent for the synthesis of oxygen-containing materials, which are sometimes reported to have interesting properties.

The product, ergosterol-5,8-endoperoxide is reported to be selectively toxic to some bacteria and viruses.

Ｐｌａｎｔａ Med., 1999, 65, 732.; Pharmazie, 1989, 44, 579; Ｐｌａｎｔａ Med., 1989, 55, 389.

HO

HO2

R

HO

H

R

1O2

Preparation of Ergosterol-5,8-endoperoxide from Ergosterol and Singlet Oxygen

Example 1

The product, 1,2-dioxetanes are widely used in numerous applications including gene expression studies, DNA sequencing, and the identification of infectious agents.

SR1

OX

SR1

OX

OO OR2

OX

OO1O2 R2OH

Lewis Acid

Synthesis of 1,2-Dioxetanes from Vinyl Sulfide and Singlet Oxygen

H. A. Tafti et al., J. Am. Chem. Soc., 1997, 119, 245.

Example 2

3. Application for Environmental Purification 　　

a. Photodegradation of Polymer 　高分子の分解

b. Photodegradation of Harmful Materials 有害物質の分解 ex) Endocrine Disruptors (Environmental Hormone)

c. Disinfection of Water and Foods 　水や食品の消毒

a. Photodegradation of Polymer

Example• Singlet oxygen has been reported to cause

photoinduced oxidative decomposition of the electro-luminescent material, BCHA-PPV.

R. D. Scurlock et al., J. Am. Chem. Soc. 1995, 117, 10194.

• The degradation is postulated to proceed via addition of singlet oxygen to the double bond in the macromolecule.

OH

OH

HO

HO

OH

OH

HO

HO

O

O

1O2

OH

OH

HO

HO

O

H

H

O

BCHA-PPV

C. Physicochemical Aspects of Molecular Oxygen and Active Oxygen Species


C. Physicochemical Aspects of Molecular Oxygen and Active Oxygen Species


この他に ROOH, ROO., RO., HOX (X=Cl, Br, I)

Electron Configuration of Mol. Oxygen

1s

2s

2p

1s

2s

2p

1s*

1s

2s

2s

2p

2p

2p

2p

Parallel Electron Spin (Triplet)

Atomic O Molecular O2 Atomic O

biradical

Electron Configuration of Singlet Oxygen and Superoxide

2s

2s

2p

2p

2p

2s

2s

2p

2p

2p

Singlet Oxygen Superoxide

Anti-parallel Electron Spin (Singlet)

1O2 O2

mono radicalanion

Physical Properties of Mol. Oxygen, Singlet Oxygen, and Superoxide

Singlet Oxygen

22.5

1.2155

96

45min(vacum)Next Table(in Solv.)

Superoxide

-9.9

1.28(KO2)

88.8

5-10min(CH3CN)1hour(DMF)

Mol. Oxygen

0

1.2074

117.9

R. Energy (kcal/mol)

Distance between twoatoms (A)

Bond Dissociation E.(kcal/mol)

Life time

Life Time of Singlet Oxygen in Various Solvents

Solvent

H2OD2O

CH3OHCD3OD

CH3COCH3CD3COCD3

Solvent

CH3CNCD3CNCHCl3CDCl3CH2Cl2CF3Cl

Lifetime/s

3.368.0

5-11.422446.5690

Lifetime/s

54.460060640105

1,000

D. Method for the Generation of Singlet Oxygen一重項酸素の発生法

D. Method for the Generation of Singlet Oxygen一重項酸素の発生法

1. Photosensitising Oxidation （光増感酸化）

2. Hydrogen Peroxide and Hypochlorite （過酸化水素と次亜塩素酸塩）

3. Heat of Organic and Inorganic Peroxides 　　（有機及び無機過酸化物の加熱）

4. Heat of Phosphine Ozonides 　　　　　　　（ホスフィンオゾニドの加熱）

5. Hydrogen Peroxide and Molybdenum Salt （過酸化水素とモリブデン塩）

E. Method for the Detection and Measurement of Singlet Oxygen

一重項酸素の検出・測定法

E. Method for the Detection and Measurement of Singlet Oxygen

一重項酸素の検出・測定法

Luminescent Analysis ( 発光分析 )1. Use of Chemical Luminous Reagents 　　

化学発光試薬の使用2. Detection of Luminescence of Singlet Oxygen

　　一重項酸素の発光の検出• The Luminescent at Visible Light Region 　　

可視光域での発光• The Luminescent at Near-IR Region

近赤外域での発光

• Near-IR region includes almost no emission arising from other species.

Prof. Suzuki et al. have recently developed two kinds

of ultra-high sensitivity instruments (TIA and CIA).

The near-IR luminescence spectroscopy is the most reliable method for the detection and measurement of singlet oxygen.


一重項酸素の応用への成功例


一重項酸素の応用への成功例

1. Deactivation of WSS Virus on Eggs Using Singlet Oxygen

　　一重項酸素による卵付着 WSS ウィルスの不活化

2. Degradation of Endocrine Disruptors (Environmental Hormone) Using Singlet Oxygen 　一重項酸素による内分泌かく乱物質（環境ホルモン）の分解

　

Examples of Endocrine Disruptors (Environmental Hormone) Degradation Using

Singlet Oxygen

1O2

Clm Cln

PCB

HC

CCl3

DDT

C

CH3

CH3

OHHO

Cl Cl

Bisphenol A

HO C9H19

Nonylphenol

Degradation

Active oxygen

Science

Transcript of Active oxygen