TY - JOUR
T1 - Conformational flexibility in the molecular structure of rotenone, a naturally occurring insecticide
AU - Rossi, M.
AU - Fule, P. Z.
AU - Taylor, M. R.
N1 - Funding Information:
The authors gratefully acknowledge the help and support of the members of the crystallographic laboratories at ICR, particularly Dr. J. Glusker and Dr. H. Berman for the use of equipment. From Flinders University, we thank Dr. C. Schiesser for help with the use of the MM2 program and Dr. M. Thompson for useful conversations and are grateful for a visiting research fellowship grant to M.R. This research was supported by National Science Foundation Grant Rll-8300122 and Grant 16970-GB4 Type G of the Petroleum Research Fund of the American Chemical Society to M.R. In addition, American Cancer Society Grants BC-132 and BC-242, National Institutes of Health Grants CA-10925 and CA-27780, and an appropriation from the Commonwealth of Pennsylvania were responsible for the diffractometer and computer equipment used at the Institute for Cancer Research in Philadelphia.
PY - 1988/12
Y1 - 1988/12
N2 - The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2I2I2I with two molecules in the asymmetric unit; a = 8.413 (1) A ̊, b = 19.840(1), c = 23.581(1), V = 3936 A ̊3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a half-chair in I, but with C8 and C8′ on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is V-shaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3°, while in molecule II it is 88.3°. Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities.
AB - The crystal and molecular structure of rotenone, a naturally occurring insecticide with mitochondrial and mitotic spindle inhibitory properties, was determined by direct methods. The crystals were orthorhombic, space group, P2I2I2I with two molecules in the asymmetric unit; a = 8.413 (1) A ̊, b = 19.840(1), c = 23.581(1), V = 3936 A ̊3, Z = 8. The structure was refined by least-squares methods to a final R = 0.067. The two molecules in the asymmetric unit have different conformations about the junction between the nonaromatic rings B and C. Ring B is in a sofa conformation in both molecules, with a slight distortion toward a half-chair in I, but with C8 and C8′ on opposite sides of the planar part of the rings. This difference in conformation results in I having an extended (linear) shape while II is V-shaped. The more elongated conformation of the molecule (I) has not been reported in previous studies. Ring C also has opposite conformations in the two molecules. The angle between the planes formed by rings A and D in molecule I is 64.3°, while in molecule II it is 88.3°. Molecular mechanics techniques were used to determine the energy of the two conformations. These calculations, at room temperature, predict molecule II to be the more stable conformer. The highly flexible site in the B/C ring junction is also chemically very reactive. This flexibility and reactivity are further discussed in terms of rotenone's inhibitory activities.
UR - http://www.scopus.com/inward/record.url?scp=0042815663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042815663&partnerID=8YFLogxK
U2 - 10.1016/0045-2068(88)90023-5
DO - 10.1016/0045-2068(88)90023-5
M3 - Article
AN - SCOPUS:0042815663
SN - 0045-2068
VL - 16
SP - 376
EP - 387
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
IS - 4
ER -