optical activity prediction: SUMMARY



 Greetings to all the CCL subscribers,
 I'd like to thank everyone who responded to the following question about
 predicting the optical rotation of an enantiomer, and thence the
 optical activity of a mixture of enantiomers.
 A summary of the responses is attached. I've only included responses
 which directly provided information relevant to the question, but
 I am also grateful to those who responded but have not been included.
 Gratefully yours,
 Robert Topper
 *****************************************************************************
 Prof. Robert Q. Topper                  email:   topper - at - cooper.edu
 Department of Chemistry                 phone:   (212) 353-4378
 The Cooper Union                        fax:     (212) 353-4341
 51 Astor Place                          subway:  take the 6 to Astor Place
 New York, NY 10003                               and you're there!
                  http://www.cooper.edu/engineering/chemechem/
 *****************************************************************************
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 Original question:
 An organic chemist with whom I collaborate has asked me
 whether it is possible to predict the optical activity
 of a mixture of enantiomers, even semiquantitatively.
 (i.e., is the optical activity "big" or "small" for
 a given enantiomeric excess, or e.e.).
 My own search of the Internet has failed to turn up anything.
 Can anyone give us any suggestions?
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: "Dr. Mike Gilson" <gilson - at - indigo14.carb.nist.gov>
 I don't know how far along things are, but
 this topic was discussed in a recent C&E News.
 I am pretty sure the work came from Beratan's
 group at Pittsburgh.
 Good luck,
 Mike
 ------------------------------------------------------------------------------
 Michael K. Gilson, Ph.D., M.D.                         Phone:   (301) 738-6217
 Center for Advanced Research in Biotechnology          Fax:     (301) 738-6255
 National Institute of Standards and Technology
 9600 Gudelsky Drive	        http://www.carb.nist.gov/carb/gilson.html
 Rockville, MD  20850-3479       e-mail: gilson - at - carb.nist.gov
 ------------------------------------------------------------------------------
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: James T Metz <METZ_JAMES_T - at - LILLY.COM>
 Robert,
      See Kondru, R.K. et al. JACS (1998) 120, 2204.  The ab initio program
 DALTON was used to estimate optical activity for chiral fragments of a natural
 product by calculation of the electric dipole magnetic dipole polarizability
 tensor.
                               Jim Metz
                               Metz_James_T - at - Lilly.com
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: "James G. Macmillan" <macmillan - at - uni.edu>
 (First of two messages)
 Robert,
 Is the question "Can you predict the rotation of a chiral molecule from
 it's
 structure?" or "Can you predict the rotation of a mixture of
 enantiomers?"?
 The first question is very difficult and I can not help you with it.  I
 believe there are theoreticians working on the problem but I am not up on
 how good they have gotten in predicting rotation of chiral molecules.
 The second question is straight forward.  The rotation of a mixture of
 enantiomer is given as the sum of the rotation of each enatiomer times its
 mole fraction. I am sure you know this.  It would mean for an enantiomer
 with a rotation of +20 that contained 20% the other enantiomer the solution
 rotation would be .2 (-20) + .8 (+20) = +12.  Of coarse, a 50/50 mixture
 would have zero rotation. .5(-20) + .5(+20) = 0.
 Jim
 > From: TOPPER ROBERT [mailto:topper - at - cooper.EDU]
 >
 >
 > Yes, the former. Or, said another way, how can you predict the
 > ROTATION of a particular enantiomer? (+20 and -20 in your example).
 >
 > robert
 >
 From: "James G. Macmillan" <macmillan - at - uni.edu>
 (Second of two messages)
 Robert,
 That is a tough one.  The octant rules (Introduction to Organic
 Spectroscopy; J. B. Lambert, H. F. Shurvell, D. Lightner, and R. G. Cook;
 page 271- 274, Macmillan Pub. Co. 1987) allow you to make a prediction on
 the sign of the CD curve.  These rule can also be found in C. Djerassi,
 Optical Rotatory Dispersion, McGraw Hill, New York, 1960.  Again, these are
 empirical rules not theoretical based.
 Jim
 **********************************************
 James G. Macmillan, Ph.D.
 Department of Chemistry
 University of Northern Iowa
 Cedar Falls, IA 50614-0423
 Ph: (319) 273-2476 FAX: (319) 273-7127
 E-mail: macmillan - at - uni.edu
 ICQ: 10405682
 ********************************************
 "Where good wine flows so does good conversation"
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: Karl Irikura <karl.irikura - at - nist.gov>
 Hi.  Have you checked recent papers by Dave Beratan?  I think he has
 had some success, using CADPAC as the basic tool.
 Good luck,
 Karl I.
 ----------------------------------------------
 Dr. Karl K. Irikura
 National Institute of Standards and Technology
 100 Bureau Drive, Stop 8380
 Gaithersburg, MD  20899-8380
 voice: 301-975-2510	fax: 301-869-4020
 e-mail: karl.irikura - at - nist.gov
 http://www.nist.gov/compchem/
 ----------------------------------------------
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: Iraj Daizadeh <daizadeh - at - fas.harvard.edu>
 Dear Professor Topper:
 I refer you to a recent paper from a group from U-Pitts; references for
 the question you pose may be addressed there.  If not; the paper is still
 a very good read.
 Kondru, RK; Wipf, P; Beratan, DN.
 Atomic contributions to the optical rotation angle as a quantitative probe
 of molecular chirality. SCIENCE, 1998 DEC 18, V282 N5397:2247-2250.
 Best regards,
 Iraj.
 Iraj Daizadeh, Ph. D.
 Harvard University
 Department of Cellular and Molecular Biology
 The Biological Laboratories, Box #140
 16 Divinity Avenue
 Cambridge, MA 02138
 Phone: (617) 495-0783
        (617) 495-0560
 Fax:   (617) 496-4313
 Email: daizadeh - at - fas.harvard.edu
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: cramer - at - pollux.chem.umn.edu (Christopher Cramer)
 Robert,
 Beratan at Pitt has published on prediction of optical rotations.
 Several references are on his web page
 (http://www.chem.pitt.edu/faculty/beratan.html)
 Chris
 Christopher J. Cramer
 University of Minnesota
 Department of Chemistry
 207 Pleasant St. SE
 Minneapolis, MN 55455-0431
 --------------------------
 Phone:  (612) 624-0859 || FAX:  (612) 626-2006
 cramer - at - pollux.chem.umn.edu
 http://pollux.chem.umn.edu/~cramer
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: "Christoph M. Koelmel" <koelmel - at - intsim.com>
 Hi,
 enantiomers have opposite specific rotations (rotation angle normalized
 with respect to length of path light has to go through and concentration
 of the substance that is optically active), and if one assumes small
 concentrations, the
 rotation angle is then just proportional to the
 difference of the concentrations of the two enantiomers, I would think.
 http://www.scimedia.com/chem-ed/spec/molec/polarim.htm might
 be useful.
 A different question is how to compute the specific rotation for an
 enantiomer.
 The DALTON program site, e.g. at http://ithaka.ki.ku.dk/QC/dalton/Master.html
 may be a useful starting point.
 Cheers,
 Christoph
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: Huub van Dam <h.j.j.vandam - at - dl.ac.uk>
 Hello Robert,
 As far as I know the optical activity of a mixture of enantiomers is just a
 linear interpolation of the optical activities of the pure enantiomers. Here
 optical activity means the amount by which the plane of polarisation of linearly
 polarised light is rotated by the optical active species.
 Another measure is related to circulardichroism. In this case the spectra of
 enantiomers are measured using circularly polarised light. Depending on the
 enantiomer and the direction of polarisation the spectra show remarkable
 differences.
 The circulardichroism spectra can be calculated by a few programs. For example
 Stefan Grimme has a DFT code that seems to obtain very accurate results, his
 webpage is at
     http://pcgate.thch.uni-bonn.de/tc/grimme.html
 you may want to look up a few of his papers.
 Kind regards, Huub van Dam
 =============================================================
 Huub van Dam                               E-mail: h.j.j.vandam - at - dl.ac.uk
 CCLRC Daresbury Laboratory                  phone: +44-1925-603362
 Daresbury, Warrington                         fax: +44-1925-603634
 Cheshire, UK
 WA4 4AD
 =============================================================
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: "Dr. S. Shapiro" <toukie - at - zui.unizh.ch>
 Dear Sir;
      There are all sorts of rules relating to the prediction of optical activity
 of enantiomers.  Some of these you may find in Caldwell & Eyring's "The
 Theory
 of Optical Activity", though this is rather dated.  From what I remember
 the
 best predictions of optical activity are in the IR range rather than, say, at
 the sodium D-line.  For further details, please consult a brief review article
 in Enantiomer 1: 151-166 ('96), an article entitled "Chemical and
 spectroscopic
 methods for determining absolute configurations of chiral alcohols".
 Tschuess,
 S. Shapiro
 toukie - at - zui.unizh.ch
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 From: "Frank J. Devlin" <devlin - at - usc.edu>
 Hi Robert,
 Take a look at Beratan's article in Science, 282, 2247 (1998).
 Regards,
 Frank Devlin.
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 From: Craig Burkhart <cburkhart - at - goodyear.com>
 Robert,
 There was an article in a recent Chemical & Engineering News (within the
 last
 month) where there was a brief about the calculation of absolute optical
 rotation. To my knowledge, this was the first ab initio ("ab initio"
 in this
 sense not necessarily meaning quantum chemical) prediction of optical rotation.
 This has been a topic that has come up, off-and-on, throughout the last few
 years. I have always said, "I don't know how to do that"; but it
 appears that it
 may now be possible. So rifle through your most recent C&E News magazines
 and
 you will find it (or search for it online on the ACS web site).
 Craig
 xxxxxxxxxxxxxxxxxxxxxxxxxx
 From: Ricardo Nunez <rnunez - at - dali.eis.uva.es>
 Dear all,
 	Our group have developed a method to calculate the
 optical activity from molecular geometry, I give you some
 references:
 J. Mol. Struct., vol. 354, (1995) 81-87
 J. Mol. Struct., vol. 442, (1998) 135-143
 J. Mol. Struct., vol. 447, (1998) 127-133
 Ricardo Nunez Miguel
 rnunez - at - sorolla.eis.uva.es
 Departamneto de Quimica Organica
 ETS de Ingenieros Industriales
 Universidad de Valladolid
 Spain