RESUMO
Oxidative degradation products of bilirubin (BOXes) are biologically highly active and certain BOXes cause long-lasting narrowing of cerebral blood vessels presumably with a significant role in subarachnoid hemorrhage. Due to the fact that mode of action as well as fate of these BOXes is widely unknown, larger amounts of these bilirubin degradation end products are required. The total synthesis of colorless (Z)-3-(5-(2-amino-2-oxoethylidene)-4-methyl-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX C) succeeds via a seven-step procedure with a total yield of 20%. Its isomeric form (Z)-3-(2-(2-amino-2-oxoethylidene)-4-methyl-5-oxo-2,5-dihydro-1H-pyrrol-3-yl)propanoic acid (BOX D) can be prepared via a five-step protocol with a yield of 30%. NMR and crystallographic studies reveal that charge delocalization within the conjugated π-systems of BOXes C and D is negligible. Exposure of solutions of Z-BOX C and Z-BOX D to bright sunlight leads to Z/E-isomerization and mixtures of the respective E/Z-BOXes C and D.
RESUMO
The reaction of (OC)5MnBr with bis(3,5-dimethyl-1-pyrazolyl)methane yields [{(PzMe2)2CH2}Mn(CO)3Br] (1). The use of tridentate heteroscorpionates such as bis(3,5-dimethyl-1-pyrazolyl)acetic acid and 2,2-bis(3,5-dimethyl-1-pyrazolyl)ethanol leads to the formation of mononuclear [(OC)3Mn{(PzMe2)2CH-CO2}] (2) and [(OC)3Mn{(PzMe2)2CH-CH2OH}]Br (3, CORM-ONN1). Salt-like photoCORM 3 is soluble in aqueous media up to a concentration of 200 µM, non-toxic up to an approx. 65 µM solution and releases all carbonyl ligands upon irradiation. The molecular complexes 1 and 2 are insoluble in aqueous solutions. CORM-ONN1 (3) slowly degrades in methanol yielding iCORM 4, consisting of the complex cation [{(PzMe2)2CH-CH2OH}{(PzMe2)2CH-CH2O}Mn]+ and the [Mn(CO)5]- counter anion with the cations linked to a dimeric unit by intermolecular hydrogen bridges between the alcohol and alkoxide functionalities.