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Volumn 48, Issue 36, 2009, Pages 6708-6712

On the treatment of conformational flexibility when using residual dipolar couplings for structure determination

Author keywords

Eckart conditions; Motional averaging; NMR spectroscopy; Residual dipolar coupling; Structure elucidation

Indexed keywords

ECKART CONDITIONS; MOTIONAL AVERAGING; NMR SPECTROSCOPY; RESIDUAL DIPOLAR COUPLING; STRUCTURE ELUCIDATION;

EID: 70349778983     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200902398     Document Type: Article
Times cited : (65)

References (57)
  • 4
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    • For some recent reviews of the use of RDCs in biomolecular NMR spectroscopy, see
    • For some recent reviews of the use of RDCs in biomolecular NMR spectroscopy, see: M. Blackledge, Prog. Nucl. Magn. Reson. Spectrosc. 2005, 46, 13-61;
    • (2005) Prog. Nucl. Magn. Reson. Spectrosc , vol.46 , pp. 13-61
    • Blackledge, M.1
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    • and references therein
    • C.M. Thiele, Concepts Magn. Reson. 2007, 30A, 65-80, and references therein.
    • (2007) Concepts Magn. Reson , vol.30 A , pp. 65-80
    • Thiele, C.M.1
  • 10
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    • and references therein
    • C.M. Thiele, Eur. J. Org. Chem. 2008, 5673-5685, and references therein.
    • (2008) Eur. J. Org. Chem , pp. 5673-5685
    • Thiele, C.M.1
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    • Angew. Chem. Int. Ed. 2006, 45, 4455-4460.
    • (2006) Angew. Chem. Int. Ed , vol.45 , pp. 4455-4460
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    • Angew. Chem. Int. Ed. 2008, 47, 2032-2034.
    • (2008) Angew. Chem. Int. Ed , vol.47 , pp. 2032-2034
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    • Angew. Chem. Int. Ed. 2008, 47, 37223726.
    • Angew. Chem. Int. Ed. 2008, 47, 37223726.
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  • 22
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    • This nomenclature of course depends on the absolute configuration. Herein we refer to the structures as depicted in Scheme 1
    • This nomenclature of course depends on the absolute configuration. Herein we refer to the structures as depicted in Scheme 1.
  • 23
    • 70349941730 scopus 로고    scopus 로고
    • The order tensor relates the laboratory frame of reference to a molecular-fixed-axis frame. The tensor accounts for averaging and is comprised of the elements Sαβ
    • The order tensor relates the laboratory frame of reference to a molecular-fixed-axis frame. The tensor accounts for averaging and is comprised of the elements Sαβ.
  • 24
    • 14944346562 scopus 로고    scopus 로고
    • Avery instructive collection of orienting properties can be found in
    • Avery instructive collection of orienting properties can be found in: F. Kramer, M. V. Deshmukh, H. Kessler, S. J. Glaser, Concepts Magn. Reson. 2004, 21A, 10-21.
    • (2004) Concepts Magn. Reson , vol.21 A , pp. 10-21
    • Kramer, F.1    Deshmukh, M.V.2    Kessler, H.3    Glaser, S.J.4
  • 25
    • 70349926342 scopus 로고    scopus 로고
    • In the meantime, we were also able to synthesize the other diastereoisomer as a racemate in its p-methoxybenzyl-protected form, With both diastereoisomers in hand, the relative configuration can even be assigned on the basis of qualitative NOESY
    • In the meantime, we were also able to synthesize the other diastereoisomer as a racemate (in its p-methoxybenzyl-protected form). With both diastereoisomers in hand, the relative configuration can even be assigned on the basis of qualitative NOESY
  • 26
    • 70349941721 scopus 로고    scopus 로고
    • is was moved into the averaging bracket so that it was also possible to account for intramolecular flexibility.
    • is was moved into the "averaging bracket" so that it was also possible to account for intramolecular flexibility.
  • 27
    • 70349912881 scopus 로고    scopus 로고
    • is is also averaged by small-amplitude vibrational motion, which would require additional vibrational corrections. This motion is usually neglected when dealing with RDCs; see, however, Refs. [23, 24] and references therein.
    • is is also averaged by small-amplitude vibrational motion, which would require additional vibrational corrections. This motion is usually neglected when dealing with RDCs; see, however, Refs. [23, 24] and references therein.
  • 30
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    • It has been noted that this approach might not be justified in all cases: A. D. Buckingham, E. E. Burnell, C. A. de Lange, Mol. Phys. 1969, 16, 299-302
    • It has been noted that this approach might not be justified in all cases: A. D. Buckingham, E. E. Burnell, C. A. de Lange, Mol. Phys. 1969, 16, 299-302.
  • 32
    • 0041342985 scopus 로고    scopus 로고
    • So far there appears to be only one reported example of the shifting of the conformational equilibrium by the orienting medium: P. Berthault, D. Jeannerat, F. Camerel, F. A. Salgado, Y. Boulard, J.-C. P. Gabriel, H. Desvaux, Carbohydr. Res. 2003, 335, 1771-1785
    • So far there appears to be only one reported example of the shifting of the conformational equilibrium by the orienting medium: P. Berthault, D. Jeannerat, F. Camerel, F. A. Salgado, Y. Boulard, J.-C. P. Gabriel, H. Desvaux, Carbohydr. Res. 2003, 335, 1771-1785.
  • 33
    • 70349910784 scopus 로고    scopus 로고
    • A population scan (as in Figure 1) performed for arbitrarily oriented conformers by using one common order tensor (see the Supporting Information) illustrates the necessity of a physically sound transformation of coordinates.
    • A population scan (as in Figure 1) performed for arbitrarily oriented conformers by using one common order tensor (see the Supporting Information) illustrates the necessity of a physically sound transformation of coordinates.
  • 34
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    • C. Eckart, Phys. Rev. 1935, 47, 552-558.
    • (1935) Phys. Rev , vol.47 , pp. 552-558
    • Eckart, C.1
  • 39
    • 70349944851 scopus 로고    scopus 로고
    • Equation (2) has the same meaning as that presented in Ref. [12]. The population used in that study, however, was extracted from J coupling constants and was not varied.
    • Equation (2) has the same meaning as that presented in Ref. [12]. The population used in that study, however, was extracted from J coupling constants and was not varied.
  • 40
    • 70349918977 scopus 로고    scopus 로고
    • Owing to symmetry, the number of independent order parameters can also be smaller than five
    • Owing to symmetry, the number of independent order parameters can also be smaller than five.
  • 41
    • 70349899443 scopus 로고    scopus 로고
    • To ensure that we had well-defined order parameters, we checked that the rank of each directional cosine matrix was five (number of order parameters) and that its condition number was sufficiently small. These criteria were fulfilled for both diastereoisomers (1 and 2).
    • To ensure that we had well-defined order parameters, we checked that the rank of each directional cosine matrix was five (number of order parameters) and that its condition number was sufficiently small. These criteria were fulfilled for both diastereoisomers (1 and 2).
  • 42
    • 0032528033 scopus 로고    scopus 로고
    • For a q factor that does not contain experimental errors, see: G. Cornilescu, J. L. Marquardt, M. Ottiger, A. Bax, J. Am. Chem. Soc. 1998, 120, 6836-6837.
    • For a q factor that does not contain experimental errors, see: G. Cornilescu, J. L. Marquardt, M. Ottiger, A. Bax, J. Am. Chem. Soc. 1998, 120, 6836-6837.
  • 45
    • 70349896371 scopus 로고    scopus 로고
    • A cross-validation procedure was performed by removing in turn each of the 22 RDCs and performing the analysis with the remaining 21 RDCs. The results are shown in Figures SI4 (common-order-tensor approximation) and SI5 (multitensor approximation) in the Supporting Information.
    • A cross-validation procedure was performed by removing in turn each of the 22 RDCs and performing the analysis with the remaining 21 RDCs. The results are shown in Figures SI4 (common-order-tensor approximation) and SI5 (multitensor approximation) in the Supporting Information.
  • 46
    • 70349926339 scopus 로고    scopus 로고
    • In practice, the parameters are determined by constructing one large S vector containing all linearly independent order parameters in one column.
    • In practice, the parameters are determined by constructing one large S vector containing all linearly independent order parameters in one column.
  • 47
    • 70349912816 scopus 로고    scopus 로고
    • We again verified that enough independent RDCs were available by checking that the rank of the (combined) directional cosine matrix was five times the number of conformers (ten for the two conformers used in this study) and that its condition number was sufficiently small. These criteria were fulfilled for both diastereoisomers (1 and 2).
    • We again verified that enough independent RDCs were available by checking that the rank of the (combined) directional cosine matrix was five times the number of conformers (ten for the two conformers used in this study) and that its condition number was sufficiently small. These criteria were fulfilled for both diastereoisomers (1 and 2).


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