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Synthesis and Spectroscopic Characterization of 4‐Chlorophenyl Isocyanate (= 1‐chloro‐4‐isocyanatobenzene) Adducts with Amino Acids as Potential Dosimeters for the Biomonitoring of Isocyanate Exposure
Author(s) -
Möller Marianne,
Henschler Dietrich,
Sabbioni Gabriele
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19980810536
Subject(s) - chemistry , valine , amino acid , adduct , isocyanate , cysteine , glycine , tripeptide , serine , lysine , organic chemistry , stereochemistry , biochemistry , enzyme , polyurethane
Blood‐protein adducts are used as dosimeter for modifications of macromolecules in the target organs where the disease develops. The functional groups of cysteine, tyrosine, serine, lysine, tryptophan, histidine and N‐terminal amino acids are potential reaction sites for isocyanates. Especially the N‐terminal amino acids, valine and aspartic acid of hemoglobin and albumin, respectively, are reactive towards electrophilic xenobiotics. To develop methods for the quantification of such blood‐protein adducts, we treated 4‐chlorophenyl isocyanate ( 1 ) with the tripeptide L ‐valyl‐glycyl‐glycine ( 2a ) and with single amino acids yielding N ‐[(4‐chlorophenyl)carbamoyl]valyl‐glycyl‐glycine ( 3a ), N ‐[(4‐chlorophenyl)carbamoyl]valine ( 3b ), N ‐[(4‐chlorophenyl)carbamoyl]aspartic acid ( 3c ), N ‐(4‐chlorophenyl)carbamoyl glutamic acid ( 3d ), N ‐acetyl‐ S ‐[(4‐chlorophenyl)carbamoyl]cysteine ( 3e ), and N ‐acetyl‐ O ‐[(4‐chlorophenyl)carbamoyl]serine ( 3f ), N α ‐acetyl‐ N ε ‐[(4‐chlorophenyl)carbamoyl]lysine ( 3g ). For several chemicals, it was shown that blood‐protein adducts are good dosimeters of exposure and dosimeters for the target dose. The hydrolysis of the N‐terminal adducts of isocyanates release hydantoins which can be separated from the rest of the protein and analyzed using GC/MS or HPLC. This was achieved with 3a . The released hydantoin could be analyzed using GC/MS. We propose to analyze the N‐terminal adducts of isocyanates with blood protein to distinguish between arenamine and arylisocyanate exposure.