Structure–activity studies of β-carbolines. 1. Molecular structure and conformation of <i>cis</i>-3-carboxylic acid-1,2,3,4-tetrahydroharmane dihydrate

Codding, Penelope W.

doi:10.1139/v83-092

Cited by 35 publications

(13 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…intensity data measurements were as described previously (12). Systematic absences of (hkl), h + k = 2n + 1; (hOl), 1 = 2n + 1; and the symmetry of the diffracted intensities identified the space group as 'Author to whom correspondence should be addressed.…”

mentioning

confidence: 99%

Studies of the dihedral angle of a crowded diselenide by X-ray crystallography and ultraviolet spectroscopy

Back¹,

Codding²

1983

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

, 2749 (1983). Bis(di-tert-butylmethyl) diselenide (4) is the first example of a diselenide with an abnormal obtuse dihedral angle resulting from steric crowding. Its value was determined to be 112.1(3)" by X-ray crystallography, as compared with typical dihedral angles of 74-87" for other diselenides. The uv spectrum of 4 supports a similar conformation in solution. ence for conformations where the dihedral angle (C-Se-Se/ Se-Se-C) ( Fig. 1) is acute and lies within the range of 74"-87", except when constrained by the imposition of a cyclic structure. Thus, the cyclic diselenide 2 displays a dihedral angle of only 56" (7).The effects of very bulky substituents on the conformations of diselenides have not been investigated by crystallographic methods. To our knowledge, even the most hindered diselenide with a known crystal structure, bis(diphenylmethy1) diselenide (3), exhibits a normal, acute dihedral angle of 82" (2). More recently, Barton and co-workers (8) reported the preparation of bis(di-tert-butylmethyl) diselenide (4), a stable, crystalline substance. An examination of a model of this compound indicated that steric interactions might be severe enough to result in significant departure from the usual preferred diselenide geometry. Steric congestion could be relieved either through an increase in the dihedral angle or by lengthening of the bonds in the C-Se-Se-C moiety. It is also interesting to note that the analogous triselenide 5, whose crystal structure has been reported (9), displays normal C-Se and Se-Se bond lengths and moderate extension of the two C-Se-Se/Se-Se-Se dihedral angles to 100.6" and 86.9". It is evident, however, that FIG. I . Conformation of a typicaI diselenide.the interposition of the third contiguous selenium atom. To ascertain the extent of such effects in diselenide 4, we undertook its X-ray crystallographic structure determination. We now report the first example of a diselenide with an obtuse dihedral angle. Since molecular conformations may differ in the solid state and in solution, we also endeavoured to confirm that diselenide 4 has an abnormal dihedral angle in solution. Compression of the dihedral angle from the preferred value of 74-87" raises the energy of the ground state of a diselenide but has little effect on the excited state (10). Thus, cyclic diselenides such as 2 exhibit strong bathochromic shifts as a result of the lowered excitation energy (1 1). A similar phenomenon might be expected in the case of a diselenide in which destabilization of the ground state results from the enlargement rather than the compression of the dihedral angle, although such an effect has not yet been documented. We believe that diselenide 4 constitutes the first such example, as it displays a marked bathochromic shift compared to other, less crowded acyclic diselenides.any steric effects resulting from the interaction of the bulky Experimental substituents are greatly reduced in the triselenide Bis(di-tert-butylmethyl) diselenide (4) was by the method of Barton and co-workers (8) int...

show abstract

mentioning

confidence: 99%

Studies of the dihedral angle of a crowded diselenide by X-ray crystallography and ultraviolet spectroscopy

Back¹,

Codding²

1983

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In summary, analysis of this structure and the previous one in this series (9) has led to the identification of a hydrogen bond acceptor site as a part of the receptor binding features of P-carbolines. This site has not been identified in the model of P-carboline binding (8).…”

Section: Resultsmentioning

confidence: 74%

“…This coplanarity is evidence for an extensive delocalization of electrons throughout the entire T system of the P-carboline and carboxyamide group. In contrast, in the tetrahydroharmane molecule (9), the angle between the plane of the indole fragment and the carboxylic acid fragment was 58.9".…”

Section: Resultsmentioning

confidence: 85%

“…O(32) angle is 154(2)". In paper 1 of this series (9) it was reported that the carboxylic acid derivative of P-carboline has extensive hydrogen bonding as part of the crystal environment. In both of these examples of oxygen-substituted side chain at position 3 of the P-carboline ring is necessary for maximal activity at the benzodiazepine receptor, it would appear that hydrogen-bond formation must be part of the interaction with the receptor.…”

Section: Resultsmentioning

confidence: 99%

“…Coutts, Micetish, and 1133 observed, p = 0.94 cm-'. Lattice and space group determination and data collection procedures were as described previously (9). Lorentz and polarization corrections were applied.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Structure–activity studies of β-carbolines. 2. Crystal and molecular structures of N-ethyl-3-carbamoyl-β-carboline

Muir¹,

Codding²

1984

Can. J. Chem.

Self Cite

View full text Add to dashboard Cite

The crystal and molecular structures of N-ethyl-3-carbamoyl-β-carboline, C14H13N3O, a synthetic ligand of the benzodiazepine receptor are reported. The space group is C2/c with a = 16.220(4), b = 7.728(4), c = 19.623(6) Å, β = 104.16(1)°, Z = 8. The carboxyamide side chain assumes an extended conformation and is almost coplanar with the β-carboline skeleton. The observed molecular conformation is compared to the current model for the receptor binding site. Hydrogen bonding and aromatic ring stacking determine the molecular packing arrangement.

show abstract

Struktur‐Wirkungs‐Beziehungen bei Nefopamhydrochlorid

Klüfers

Petersenn

Röder

1986

Archiv der Pharmazie

View full text Add to dashboard Cite

Die an (+)-Nefopamhydrochlorid (1) durchgefiihrte Rontgenstrukturanalyse (P2,/c, a = 1176,1, b = 773,9, c = 1689,7pm, fi= 97,43", Z = 4) zeigt, da8 der Heterocyclus aus zwei einfachen Strukturelementen zusammengesetzt ist. Fiinf Atome (2,3,4,5 und 6) haben die Anordnung eines Cyclohexan-Fragmentes; zugleich liegen fiinf Atome (2, 1, 10a, 6a und 6) in der Ebene des anellierten Benzolringes. Die beiden Benzolringe stehen, anders als bei den strukturell verwandten Benzodiazepinen, nahezu senkrecht aufeinander. Die fjbereinstimmung der Strukturen von 1 und (-)-Nefopamhydrochlorid-monohydrat wird im Hinblick auf die Starrheit der Konformation diskutiert. Nefopam kann danach als Modellsubstanz f i r Serotonin-Agonisten und -Antagonisten dienen. Als strukturelle Gemeinsamkeit dieser Verbindungen tritt eine aliphatische Aminogruppe auf, die ca. 600 pm vom Zentrum eines Aromaten entfernt etwa in dessen Ringebene liegt oder leicht in diese Position uberfiihrt werden kann. Structure-Activity Relationships of Nefopam HydrochlorideAn X-ray study of (+)-nefopam hydrochloride (1) (P2,/c, a = 1176.1, b = 773.9, c = 1689.7~1~1, = 97.43", Z = 4) shows that the heterocyclic ring has two structurally simple features: Five atoms (2-6) form the C, fragment of a cyclohexane ring, while another five atoms (2, 1,10a, 6a and 6) lie within the plane of the fused benzene ring. The two benzene rings are almost perpendicular to each other, which is remarkably different from the structurally related benzodiazepines. The structure of 1 is practically identical with that found for (-)-nefopam hydrochloride monohydrate, a fact which is discussed under the aspect of conformational rigidity. Nefopam can be taken as a model substance for serotonin agonists and antagonists. As a common structural feature these compounds have an aliphatic amino group which lies (or can be easily placed) at a distance of about 600pm from the center of the aromatic system and nearly within the plane of the system.

show abstract

Structure–activity studies of β-carbolines. 1. Molecular structure and conformation of cis-3-carboxylic acid-1,2,3,4-tetrahydroharmane dihydrate

Cited by 35 publications

References 2 publications

Studies of the dihedral angle of a crowded diselenide by X-ray crystallography and ultraviolet spectroscopy

Studies of the dihedral angle of a crowded diselenide by X-ray crystallography and ultraviolet spectroscopy

Structure–activity studies of β-carbolines. 2. Crystal and molecular structures of N-ethyl-3-carbamoyl-β-carboline

Struktur‐Wirkungs‐Beziehungen bei Nefopamhydrochlorid

Contact Info

Product

Resources

About