CARS Studies of the Photochemistry of Bilirubin and the Mechanism of the Phototherapy of Neonatal Jaundice
| Project/Area Number |
60470017
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
構造化学
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| Research Institution | Waseda University |
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Principal Investigator |
HIROAKI TAKAHASHI Waseda University, School of Science of Engineering, Professor, 理工学部, 教授 (40063622)
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| Co-Investigator(Kenkyū-buntansha) |
KOHICHI Itoh Waseda University, School of Science of Engineering, Professor, 理工学部, 教授 (40008503)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1986: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1985: ¥3,500,000 (Direct Cost: ¥3,500,000)
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| Keywords | bilirubin / CARS / Phototherapy of neonatal jaundice / 光化学 |
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| Research Abstract |
The configurational change of bilirubin dimethylester (BRE) in different solvents has been studied by infrared and resonance CARS spectroscpies. It has been shown that in nonpolar solvents like <CCl_4> , BRE forms intramolecular hydrogen bonds between the N-H groups in the pyrrole rings (also in the pyrrolinone rings) and the carboxyl groups in the side chains. Because of this intramolecular hydrogen bonding, BRE adopts the configuration in which the hydrophobic part comes outside of the molecule, a configuration which is not dissolvable in water. In contrast, in hydrogen-bond-accepting solvents like dimethylsulfoxide, BRE forms stronger hydrogen bonds to solvent molecules, which necessitates the rotation about the C-C and C=C bonds connecting the pyrrole and pyrrolinone rings, resulting in the configuration in which hydrophilic part comes outside of the molecule, a configuration which is soluble in water. The absorption spectrum of BR under light irradiation closely resembles that of BRE in hydrogen-bond-accepting solvents. This implies that the mechanism of phototherapy of neonatal jaundice may be explained as being due to the conformational change of BR by light irradiation to a water-soluble conformation similar to that of BRE in hydrogen-bond-accepting solvents.
The toxicity of BR is attributed to the binding of BR to mitocondrial membranes leading to the inhibition of the respiration of mitocondria. Serum albumin is an effective reagent for detoxyfying bilirubin. This is because serum albumin binds tightly to bilirubin and prevents bilirubin from binding to mitocondrial membranes. Therefore, the information about the binding site of bilirubin to serum albumin can be an important clue to the understanding of the mechanism of the toxcicity of bilirubin. Our resonance CARS results indicate that the binding site of bilirubin is the pirrolinone C=O groups and that the nature of the binding is their hydrogen bonds to albumin.
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Report
(1 results)
Research Products
(5 results)
