A New Class of Linear Tetrapyrroles:  Acetylenic 10,10a-Didehydro-10a-homobilirubins

Abstract

Novel bilirubin analogues with dipyrrinones conjoined to an acetylene rather than a methylene group were synthesized and examined spectroscopically. Despite the increased separation of the dipyrrinones forced by replacing a -CH(2)- by a -C(triple bond)C- unit, molecular dynamics calculations show that, like bilirubin, they may still engage in intramolecular hydrogen bonding to carboxylic acid groups when the propionic acid chains are slightly lengthened, e.g., butanoic acids. Unlike bilirubin, however, which is bent in the middle and has a ridge-tile shape, the acetylene orients the attached dipyrrinones along a linear path, and intramolecular hydrogen bonding preserves a twisted linear molecular shape. The extended planes of the dipyrrinones intersect along the -C(triple bond)C- axis at an angle of 136 degrees for the conformation stabilized by intramolecular hydrogen bonding in the bis-butyric acid rubin (1b). With shorter acid chains (propionic), only one CO(2)H can engage an opposing dipyrrinone in intramolecular hydrogen bonding, and in this energy-minimum conformation of the linear pigment 1a, the intersection of the extended planes of the dipyrrinones has an angle of 171 degrees. Spectroscopic evidence for such linearized and twisted structures was found in the pigments' NMR spectral data and their exciton UV-vis and induced circular dichroism spectra.

Homorubins and homoverdins

“…Their red-orange color gives evidence to some level of electronic interaction of the dipyrrinone chromophores through the ethene π-system. And in this case, the situation appears to be analogous to that observed when dipyrrinones are linked by an ethyne (−C≡C−) unit, which also gives red-orange solutions, as was observed previously [33]. The dehydro- b -homoverdins [19, 20] exhibited the reddish color associated with the dipyrrylmethene chromophore [30, 34] and with α-benzylidene dipyrrinones [35, 36].…”

“…In connection with our interest in centrally expanded [11, 16, 33, 35, 50–52] and contracted [53] analogs of the synthetic model (mesobilirubin-XIIIα) for the natural pigment of human bile and jaundice [1], we prepared homorubin 1 and its analog 2 , with butyric acid groups replacing propionic acids. Yellow 1 and 2 preferentially adopt folded, intramolecularly hydrogen-bonded conformations and exhibit a lipophilicity comparable to that of mesobilirubin-XIIIα.…”

Functional Porphyrinoids from a Biomimetically Decorated Bipyrrole

“…After some screening we found that the ester side chains of the manganese complex 6 can be hydrolyzed in excellent yield by the use of LiOH in a thf/ water mixture. [32] In order to avoid the demetallation and concomitant ring oxygenation of the corrole, [33] the neutralization step requires particular care and has to be carried out only after extractive workup by using glacial acetic acid. Diacid 8 is obtained in Ͼ90 % yield as a black powder and was analyzed by high resolution mass spectrometry.…”

Intramolecular hydrogen bonding and linear pentapyrrole conformation

“…The 13 C chemical shifts of the component dipyrrinones compare very favorably with those of permethylbilirubin [28], suggesting no strong perturbing interactions between the central pyrrolyl units and the flanking dipyrrinones. The low solubility of 2 in CHCl 3 made it impossible to determine its 1 H NMR spectrum in CDCl 3 , although spectra could be obtained in (CD 3 ) 2 SO (Table 1).…”

“…In bilirubins, the 1 H NMR N-H chemical shifts of the pyrrole and lactam have proven to be an excellent way to determine whether the dipyrrinone units of bilirubins are involved in intramolecular hydrogen bonding [13, 19, 20, 27, 28]. Previous studies have shown that the carboxylic acid COOH appears near 13.6 and the lactam and pyrrole N-Hs appear near 10.6 and 9.2 ppm, respectively, in CDCl 3 solvent when the dipyrrinone and carboxylic acid groups are intramolecularly hydrogen bonded, as shown in Figs.…”