Solution and biologically relevant conformations of enantiomeric 11-cis-locked cyclopropyl retinals

Yukari Fujimoto, Nathan Fishkin, Gennaro Pescitelli, John Decatur, Nina Berova, Koji Nakanishi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

To gain information on the conformation of the 11-cis-retinylidene chromophore bound to bovine opsin, the enantiomeric pair (2a and 2b) of 11-cis-locked bicyclo[5.1.0]octyl retinal (retCPr) 2 was prepared and its conformation was investigated by NMR, geometry optimization, and CD calculations. This compound is also of interest since it contains a unique moiety in which a chiral cyclopropyl group is flanked by triene and enal chromophores, and hence would clarify the little-known chiroptical contribution of a cyclopropyl ring linked to polyene systems. NMR revealed that the seven-membered ring of retCPr adopts a twist chair conformation. The NMR-derived structure constraints were then used for optimizing the geometry of 2 with molecular mechanics and ab initio methods. This revealed that enantiomer 2a with a 11β, 12β-cyclopropyl group exists as two populations of diastereomers depending on the twist around the 6-s bond; however, the sense of twist around the 12-s is positive in both rotamers. The theoretical Boltzmann-weighted CD obtained with the π-SCF-C-DV MO method and experimental spectra were consistent, thus suggesting that the conjugative effect of the cyclopropyl moiety is minimal. It was found that only the β-cyclopropyl enantiomer 2a, but not the α-enantiomer 2b, binds to opsin. This observation, together with earlier retinal analogues incorporation results, led to the conclusion that the chromophore sinks into the N-terminal of the opsin receptor from the side of the 4-methylene and 15-aldehyde, and that the binding cleft accommodates 11-cis-retinal with a slightly positive twist around C12/C13. A reinterpretation of the previously published negative CD couplet of 11,12-dihydrorhodopsin also leads to a chromophoric C12/C13 twist conformation with the 13-Me in front as in 1b. Such a conformation for the chromophore accounts for both the observed biostereoselectivity of retCPr 2a and the observed negative couplet of 11,12-dihydro-Rh7.

Original languageEnglish
Pages (from-to)7294-7302
Number of pages9
JournalJournal of the American Chemical Society
Volume124
Issue number25
DOIs
Publication statusPublished - 2002 Jun 26
Externally publishedYes

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Opsins
Conformations
Chromophores
Enantiomers
Retinaldehyde
Polyenes
Nuclear magnetic resonance
Mechanics
Aldehydes
Molecular mechanics
Geometry
Population

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Solution and biologically relevant conformations of enantiomeric 11-cis-locked cyclopropyl retinals. / Fujimoto, Yukari; Fishkin, Nathan; Pescitelli, Gennaro; Decatur, John; Berova, Nina; Nakanishi, Koji.

In: Journal of the American Chemical Society, Vol. 124, No. 25, 26.06.2002, p. 7294-7302.

Research output: Contribution to journalArticle

Fujimoto, Yukari ; Fishkin, Nathan ; Pescitelli, Gennaro ; Decatur, John ; Berova, Nina ; Nakanishi, Koji. / Solution and biologically relevant conformations of enantiomeric 11-cis-locked cyclopropyl retinals. In: Journal of the American Chemical Society. 2002 ; Vol. 124, No. 25. pp. 7294-7302.
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