The structure of bilirubin

Abstract

Crystals of bilirubin are triclinic, space group P1̄ with cell dimensions a = 19.439, b = 11.707, c = 15.500 Å, †, α = 97.19, β =100.22, γ = 118.20°, Z = 4. The structure was solved by direct methods incorporating information derived from reflexion quartets and by using a set of diffractometer data containing 1408 reflexions with F obs ≥ 3σ( F obs ). The structure was refined with bond-length constraints to a final R of 0.125 by using a set of microdensitometer-measured photographic data containing 1323 unique observed reflexions. Both data sets were collected from a matured crystal whose diffraction pattern had improved considerably during a period of several weeks. Bilirubin is shown to have the Z configuration at both the C5 and C15 bridges. The two independent molecules of bilirubin in the crystal structure have very similar ‘ridge tile’ conformations: rings (A + B) and rings (C + D) form two good planes with an interplanar angle of approximately 97° and the molecule is stabilized by six intramolecular hydrogen bonds. There is no evidence for any intermolecular hydrogen bonding. Observed bond lengths suggest that bilirubin can be regarded as a 2,2' - dipyrrolylmethane with conjugating substituents at the α positions. When freshly prepared, most crystals of bilirubin have reflexions hkl ( h odd) diffuse: this observation is discussed in terms of the molecular conformation of bilirubin and the particular packing arrangement which these molecules adopt in the crystal structure.

Structure of bilirubin IXα (isopropylammonium salt) chloroform solvate, C33H34N4O62−.2C3H10N+.2CHCl3

“…la and 2), as found in pure bilirubin IXct (Bonnett et al, 1976;Bonnett et al, 1978), in bilirubin chloroform-methanol solvate (Le Bas et al, 1977;Le Bas et al, 1980), in mesobilirubin chloroform solvate (Becker & Shcldrick, 1978) and in diethoxybilirubin diethyl ester (Sheldrick & Becker, 1979). (×10 4) and equivalent isotropic thermal parameters (A 2 × 10 3) (2) 7674 (3) 10343 (4) 4029 (4) 66 (2) C (3) 7669 (3) 9989 (4) 3361 (3) 63 (2) C (4) 7114 (3) 9263 (4) 3208 (3) 56 (2) C (5) 6960 (3) 8740 (4) 2596 (3) 55 (2) C (6) 6461 (3) 8017 (4) 2333 (3) 51 (2) C (7) 6391 (3) 7575 (4) 1655 (3) 52 (2) C (8) 5825 (3) 6911 (4) 1602 (3) 46 (2) C (9) 5569 (3) 6943 (4) 2253 (3) 50 (2) C(10) 5000 6344 (6) 2500 60 (3) C(l 1)…”

“…A valuable point of interest concerned with the structure of bile pigments, particularly bilirubin (1) is the type of their bonding with albumin and other proteins which act as carriers of the pigment in the human organism (Brodersen, 1979); thermochemical and kinetic results obtained by Jacobsen (1977) were in favour of hydrogen bonds and salt linkages. On the other hand the crystal structures of bilirubin itself (Bonnett, Davies & Hursthouse, 1976;Bonnett, Davies, Hursthouse & Sheldrick, 1978) and of its chloroform-methanol solvate (Le Bas, Allegret & de Rango, 1977;Le Bas, Allegret, Mauguen, de Rango & Bailly, 1980) do not seem to suggest an answer, all the hydrogen bonds being intramolecular. Therefore it seemed to us worthwhile to study the structure of a complex of the bile pigment with a low-weight amine, as BILIRUBIN IXa (ISOPROPYLAMMONIUM SALT) CHLOROFORM SOLVATE a model for the bilirubin-protein associations.…”

“…Moreover, the pattern of hydrogen bonds is quite different from that found in related compounds having a ridge-tile conformation. Whereas in bilirubin itself (compound A ; Bonnett et al, 1978) and in bilirubin chloroform-methanol solvate (compound B;Le Bas et al, 1980) all the hydrogen bonds are intramolecular, as are most of those in mesobilirubin chloroform solvate (compound C;Becker & Sheldrick, 1978),~ in the present complex there are only four intramolecular hydrogen bonds, each of the BILIRUBIN IXct (ISOPROPYLAMMONIUM SALT) CHLOROFORM SOLVATE * Still shorter C-C bond lengths have been reported for three ethyl groups in 3,8,12,17-tetraethyl-4,5-dimethoxy-2,7,13,18-tetramethyl-4,5-dihydrobilin-1,19(21H,24H)-dione (CuUen, Van Opdenbosch, Meyer, Smith & Eivazi, 1982).…”

Structures of (Z)-3,4-diethyl-5-(phenylmethylene)-3-pyrrolin-2-one, C15H17NO (I), and (Z)(syn)-3,4-dimethyl-5-(2-pyridylmethylene)-3-pyrrolin-2-one, C12H12N2O (II)

“…0108-2701/84/010088-05501.50 methine single bonds (Bonnett, Davies, Hursthouse & Sheldrick, 1978) (Fig. 1).…”

Methyl 4-(2-furyl)-6,8-dioxo-2,7-diphenyl-3,7-diazabicyclo [3.3.0]octane-2-carboxylate

“…Initial attempts to solve the structure with standard direct-methods programs proved unsuccessful: therefore 'trio relations' (Table 1) each containing two negative and one positive quartet were used to construct a 20 reflexion starting set (Bonnett, Davies, Hursthouse & Sheldrick, 1978). The 4096 resulting permutations were expanded by the Y2 formula and Giacovazzo, 1975): one very large or two or three fairly large cross terms indicate a positive quartet.…”