Summary of replies on NAD and hydride transfer

 Following is a summary of replies to last week's question about hydride
 transfer.
 >
 > Is anyone aware of information on transition state geometry for hydride
 > transfer to the nicotinamide ring of NAD?  I will appreciate any
 > theoretical and/or experimental info you can provide.  Thanks!
 >
 > Eric  Walters
 >
 --------------------------
 Eric,
 I do not have a specific reference, but there was some work done in this
 area by Houk and Wu (probably published in JOC).  I think I saw something
 in 1993, but I know they were working on this as early as 1989.
 Regards,
 Susan Gustafson, Ph.D.
 UniChem Support Specialist
 Cray Research, Inc.
 -----------------
 I don't know if the specific system of a pyridinium structure
 receiving a Hydride moiety from something like methanol
 (i.e. Pyridinium + methanol => Dihydropyridine + formaldehyde)
 has been theoretically studied. Orlando Tapia in Sweden had
 use a smaller prototype, a cyclopropenium cation + hydride donor
 and published something in JACS about 3-4 years ago. I don't have
 the reference. I seem to remember larger systems being dealt with
 in 1-2 papers in THEOCHEM in the last couple of years. Generally,
 however, hydride transfer reactions have not been broadly dealt
 with in ab initio theoretical chemistry. The hydride aspect
 forces one to use a diffuse basis set (H(-) itself is not even
 stable at the SCF level for any basis set, correlation is required
 to approach the known electron affinity of H atom around 0.7 eV).
 Therefore any credible ab intio calculation will probably be done
 using a 6-31++G* basis or larger, this preventing any very large
 systems from being treated.
 I, myself, in a project with a Hungarian group, looked at
 some hydride transfers related to a biologically related
 reaction of reductive amination resulting from the reaction of
 formaldehyde with ammonia, alkyl amines or free amino groups on
 amino acids.  Reductive amination is a standard reaction discussed
 in organic text books (e.g. H2C=O + NH3 => H2C(-NH2)-OH =>
 H2C=NH; followed by protonated H2C=NH reacting with H2C(-NH2)-OH
 giving CH3NH2). This is currently unpublished but the reaction
 is easy, i.e. activation energies are not large (less that about
 15 kcal/mol) for reactions which are nearly isoenergetic.
 With regard to a calculation of full model of DPNH, in a solvent
 system, this is technically out of range in ab initio calculations
 but a program like AMSOL could handle it semiempirically. Cramer
 and Trular (see Journal of Computer Aided Design, 6 (1992) 629-666)
 treat proton transfers from pyridinium, Their AMSOL program,
 new version, could generate the transition states as optimized
 in the solvent cavity. In earlier versions of the program, the
 optimizations are slow, but technically possible now. In fact,
 I would advise any ab initio calculation to be preceded by a
 semiempirical study first. The resulting semiempirical transition
 states would likely be close to the ab inito ones, although
 the formers energies are not too reliable. Doing ab initio
 calculations using a continum solvent model is a formidable
 task since the ab intio programs capable of doing so are not
 being generally distributed yet. Although massively parallel
 ab initio programs capable of handeling such a calculation are
 now being developed, I'd say we are 1-3 years away from seeing
 very many calculations coming out of these newly developing
 technology. The AMSOL program is available thorugh QCPE or
 commercially available as included in AMPAC 5 or SPARTAN. The latter
 does both ab initio and semiempirical calculations but has
 a solvent model only in the case of the latter.
 regards
 E. M. Evleth
 Dynamique des Intereactions Moleculaires.
 Universite Pierre et Marie Curie
 4 Place Jussieu, Tour 22, Paris 75240
 33-1-44-27-42-08 (work), 33 = France; 1 = Paris
 33-1-45-48-67-20 (home),FAX 33-1-44-27-41-17 (lab)
 --------------------------
         I am not sure whether you are interested in the following:
 JACS, 113, 2353 (1991); JOC, 58, 2043 (1993).  These are article by
 K. Houk and Y-D Wu.  I think they have a more recent article on this
 area.
 Ida
 ------------------------------
 Eric,
 I am doing calculations on the reaction profile in malate dehydrogenase that
 has both proton and hydride tranfer reactions.  The hydride reaction is
 from malate to the nicotinamide of NAD.  We use a combined AM1
 semiempirical/CHARMM MM Hamiltonian that I have developed.  We calculated
 the entire reaction profile for this system, which includes transition
 state geometries.
 Maybe some of our results would be useful for you??
 Paul Bash
 Argonne National Laboratory
 Bldg 202/A349
 9700 S. Cass Avenue
 Argonne, IL. 60439
 bash(-(at)-)mcs.anl.gov
 Phone: 708-252-8631 (work)
 Phone: 312-642-3029 (home) I often work at home.
 Fax: 708-252-5517
 ----------------------------------------
 Thanks to all who replied!
 Eric
 * D. Eric Walters, Ph.D., Associate Professor, Biological Chemistry
 * Finch University of Health Sciences/The Chicago Medical School
 * 3333 Green Bay Road, North Chicago, IL  60064
 * ph 708-578-3000, x-498;fax 708-578-3240; email:
 walterse(-(at)-)mis.fuhscms.edu
 * "A man would do nothing if he waited until he could do it so well that
 *  no one would find fault with what he had done." --Cardinal Newman