ABSTRACT
The anhydrous form, (I), of the title compound, (-)-2-(1,2,3,4,4a,7-hexahydro-4a,8-dimethyl-1,7-dioxo-2-naphthyl)propionic acid, C(15)H(18)O(4), derived from a naturally occurring sesquiterpenoid, has two molecules in the asymmetric unit, (I) and (I'), differing in the conformations of the saturated ring and the carboxyl group. The compound aggregates as carboxyl-to-ketone hydrogen-bonding catemers [O.O = 2.776 (3) and 2.775 (3) A]. Two crystallographically independent sets of single-strand hydrogen-bonding helices with opposite end-to-end orientation pass through the cell in the b direction, one consisting exclusively of molecules of (I) and the other entirely of (I'). Three C-H.O=C close contacts are found in (I). The monohydrate, C(15)H(18)O(4).H(2)O, (II), with two molecules of (I) plus two water molecules in its asymmetric unit, forms a complex three-dimensional hydrogen-bonding network including acid-to-water, water-to-acid, water-to-ketone, water-to-water and acid-to-acid hydrogen bonds, plus three C-H.O=C close contacts. In both (I) and (II), only the ketone remote from the acid is involved in hydrogen bonding.
ABSTRACT
The hemihydrate of the title diketo acid, C(24)H(36)O(4).0.5H(2)O, forms hydrogen-bonded carboxyl dimers related by a C(2) axis at crystallographic sites on the a and b edges of the chosen cell [O.O = 2.643 (7) and 2.716 (7) A]. The ketone ends of the molecules approach each other at sites near ((1/2),(1/2),(1/2)), ((1/2),0,(1/2)), (0,0,(1/2)) and (0,(1/2),(1/2)) in an interleaved arrangement incorporating partial-occupancy water hydrogen bonded to the B-ring ketone.
ABSTRACT
The crystal structure of (+/-)-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (C(11)H(10)O(3)) involves projection of the carboxyl group nearly orthogonal to the aromatic plane and hydrogen bonding of the acid groups by centrosymmetric pairing across the a edge and the center of the chosen cell [O...O = 2.705 (2) A]. Intermolecular C--H...O==C close contacts to translationally related molecules are found for both the ketone (2.55 A) and the acid (2.67 A). In (+/-)-1-oxo-1,2,3,4-tetrahydronaphthalene-2-acetic acid (C(12)H(12)O(3)), the aggregation involves centrosymmetric carboxyl dimers mutually hydrogen bonded across the bc face and the a edge of the chosen cell [O...O = 2.674 (2) A]. A 2.60 A close C--H...O==C contact is found to the carboxyl group of centrosymmetrically related molecule.
ABSTRACT
In the monohydrate of the title compound, (+)-2beta, 4aalpha-dihydroxy-1,7-dimethyl-8-oxo-4bbeta,7alpha- gibbane-1alpha, 10beta-dicarboxylic acid-1,4a-lactone, C(19)H(24)O(6).H(2)O, intermolecular hydrogen bonding progresses helically along b from carboxyl to ketone [O...O = 2.694 (5) A]. The carboxyl and lactone carbonyl groups in translationally related molecules within a helix both accept hydrogen bonds from the same water of hydration. The oxygen of this water in turn accepts a hydrogen bond from the hydroxyl group of a third screw-related molecule in an adjacent counterdirectionally oriented helix, yielding a complex three-dimensional hydrogen-bonding array. Intermolecular O...H-C close contacts were found to the carboxyl and lactone carbonyls, the hydroxyl, and the water.
Subject(s)
Diterpenes/chemistry , Gibberellins/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Molecular Structure , StereoisomerismABSTRACT
BACKGROUND & AIMS: Gain-of-function trypsin mutations cause acute pancreatitis and chronic pancreatitis. Loss of trypsin inhibitor function may have similar effects. We investigated the prevalence of SPINK1 (PSTI) mutations in familial pancreatitis, idiopathic chronic pancreatitis, and controls. METHODS: Genetic-linkage studies were performed in 5 familial pancreatitis families. The entire SPINK1 gene was sequenced in 112 affected individuals and 95 control DNA samples, and exon 3 was sequenced in 95 additional controls. X-ray crystallography-based model building and statistical studies were performed. RESULTS: Significant linkage between pancreatitis and 5q31.1-2 was excluded. Novel SPINK1 mutations, one D50E mutation, one IVS3+125 C>A, and five IVS3+184 T>A intronic polymorphisms were identified. The N34S and P55S mutations were observed in 29 of 112 patients (25%) as N34S/N34S (n = 7), N34S/wt (n = 19), N34S/P55S (n = 2), and N34S/D50E (n = 1). Three hundred eighty control alleles revealed 3 N34S (0.77%), 2 P55S (0.53%), and no D50E mutations. Age of disease onset and severity were similar between homozygous and heterozygous patients. Structural modeling revealed several possible pathophysiologic mechanisms for the N34S mutation. CONCLUSIONS: SPINK1 mutations are common in the population (approximately 2%), but are clearly associated with pancreatitis. The mutation-associated risk is low. Modeling and familial clustering suggest that SPINK1 mutations are disease modifying, possibly by lowering the threshold for pancreatitis from other genetic or environmental factors, but by themselves do not cause disease.
