Subject: Re: CCL:TM force fields

From: News user <[email-masked]>
Date: Tue, 1 Aug 2000 20:02:47 -0500 (CDT)

On Tue, 1 Aug 2000, Isaac B. Bersuker wrote:

> 
> All this together makes imposible to get reasonable parametrization of
> a force field (with transferable parameters) that could be used in
> modeling similar to that of organic and/or non-TMS, in general.
> 
> I am sorry that these important features of TMS remain unknown to
> people engaged in their investigation.
> 

 While I am an outsider to this field of chemistry, I could not help but
comment on the above. Dr. Bersuker states that it is not possible to
design a general force field which will work equally well in all the TMS
compounds. While nobody argues with this generalization, I do not think
that the generalization allows one to conclude that no force field works
in any class of TMS compounds no matter how small this class is.

 The other posters were talking exactly about such narrow class of TMS
compounds, where useful parametrization was obtained, applied to other
similar TMS compounds, and documented in the literature. 

 In the light of the above, what is then the substance of Dr. Bersuker's
critisism of the work that other people do ?

 Sincerely,
 Konstantin Kudin

---

From: Robert K Szilagyi <[email-masked]>
Date: Tue, 01 Aug 2000 18:10:20 -0700

Dear Prof. Bersuker,
as a fellow, who was quite engaged in developing molecular mechanical
force fields for transition metal complexes (especially mononuclear
organometallic complexes, which have well-defined structures and have
catalytic importance - in my case in olefin metathesis and
polymerisation) 
Reading your previous email, I would like to point out one important
aspect of using MM model chemistries.

You have listed very important features of transition metal systems
(cis/trans effect; donation/back donation; JT effects), which are
indisputable are the major factors determining the molecular structure
and reactivity of such systems, but they all related to the electronic
structure or wavefunction. 
In the MM models *** THERE ARE NO ELECTRONS*** and no one is expecting
any insight about the electronic structure of the wavefunction,
otherwise it would be a complete abuse of the method.

Users of the MM methods are interested in something else. May I term
this: the result of all those effect you have mentioned (and many
others, of course). Their superposition, as it, is manifested in the
molecular structure.

During the MM parameter development, experimental steric information
(internal coordinates) are given as starting point supplied with
experimental force constants, which than adjusted in order to reach as
good agreement as possible between the experimental and calculated
structures. I would like to emphasise the word STRUCTURE quite much. 

How would you consider a case study of the following reaction mechanism
carried out by MM? For example, asymmetric synthesis by a TM complex
with huge, chiral, sterically crowded phosphine/phosphite ligands
(BINAPHOS, etc.), where all the intermediates of the reaction pathway
are very well understood experimentally. Each intermediate isolated and
characterised separately and all the transition states (at least the
activation barriers) are established by kinetical measurement. As far as
I know in most cases the rate determining step is the substrate
coordination, which is allowed in certain orientation. This specificity
is the origin of any stereo-/regio-/enantio-selectivity. 
Let's be honest, in such an ideal case, doing quantum chemical
calculation does not give more insight, other than a nice way of method
calibration. BUT, if we would like to optimise the catalyst system -
that is a different story: design of new phosphine ligands and study the
effect of various substitutions of quite a few variation (referring here
to combinatorical chemistry approaches, structural libraries, etc). 

Cannot we use a very precisely parameterised MM force field of an
intermediate and compare the relative energies of various derivatives
STRICKLY KEEPING THE SAME SET OF ATOM AND BOND TYPES around the TM
centre? 
What would be your reaction as a referee of such a research paper or
research proposal? 

I hope I'm not going to offend you by my lines and sorry for the long
email, but I wanted to be very clear!

I very much interested in your reply!
Best wishes from Stanford,
Robert
 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
   Robert K. SZILAGYI, PhD        postdoctoral fellow
   Department of Chemistry        
   (Solomon Group-Room OC105)  	  Phone: +1 650 723 0041
   Stanford University            Fax:   +1 650 725 0259
   333 Campus Drive               Email: [email-masked]
   Stanford CA 94305-5080	  ICQ:   [email-masked]
 ======================================================================
  ********** All opinions are my own, NOT my employer's ! **********
 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

---

From: Luigi Cavallo <[email-masked]>
Date: Wed, 2 Aug 2000 15:43:00 +0000 (GMT)

Hi, just to add my 2 cents to the discussion.

I substantially agree with P-O Norrby and with R K Szilagy.

I have been working many years with pure MM methods on the stereo- and 
regioselectivity in the polymerization of 1-alkenes with  heterogeneous
and homogeneous Ziegler-Natta catalysts. 

A few years ago, to make such calculations you had to "guess"  several
force field parameters, or just fix some internal  coordinates to
"reasonable" values. Although quite rude, the approach has worked.

In the last few years, however, several research groups developed  MM
force fields for metallocenes, and now the MM calculations on  these
systems can be done without any "guess" or fixing of internal coordinates.

Force fields for metallocenes can be found in:

    Doman et al     JACS            1992, 114, 7264
    Hollis et al    Organometallics 1993, 12, 3385
    Doman et al     JACS            1995, 117, 1352
    Howler et al    Organometallics 1994, 13, 2380    

Good resumes on the applications can be found in:

    Resconi et al   Chem Rev 2000, 100, 1253
    Angermund et al Chem Rev 2000, 100, 1457

The improvements of MM force fields for TM complexes has been rather good
in the last years. And the results obtained with such developments are
there to witness the validity of such approaches. Clearly, people have to
know what CAN be done and what CANNOT be done with MM.

In the post of Szilagy, the applicability of such methods is briefly but
correctly reviewed.

Regards,

Luigi

--------------------------------------------------------------------------
| Dr. Luigi Cavallo                                Dept. of Chemistry    |
| Ph:  ++39-81-2536635                             Univ. of Naples       |
| Fax: ++39-81-5527771                             Via Mezzocannone 4    |
| Email [email-masked]                 I-80134 Napoli, ITALY |
--------------------------------------------------------------------------

---

From: "Isaac B. Bersuker" <[email-masked]>
Date: Wed, 02 Aug 2000 12:33:33 -0700

Dear Dr Szilagyi:

Thank you for your message. Your statements seem to be correct except in one point:
you miss the NONTRANSFERABILITY (NT) of the force field parameters (FFP) from one
compound to another which deprives the whole approach of its heuristic value.

The NT emerges from the fact that in TMS the parameters for the M-L1 bond depend
very strongly on the presence of other M-L2, M-L3,..., bonds. For instance, the
Cu-O bond length varies between 1.8 A and 3.0 A dependent on other bonds and the
next coordination sphere in the TMS (see my 1996 book). What bond length Cu-O would
you take as a FFP?

I also state in the book above that in very LIMITED CASES when all the bonds remain
the same (and the next coordination sphere is not very intrusive) some versions of
MM modeling may be useful. These special conditions should be carefully specified
and checked. Unfortunately, people use the MM scheme without any discussion of
these important limitations.

I understand that you ask me what to do with large TMS if  not modeling by means of
MM. My answer is to use combined QM/MM methods in which the metal site is treated
by QM, while the huge environment is modeled by MM. Of course, this approach is not
simple and not strightforward (no serious science is strightforward), see, e.g., in
Combined QM/MM Methods, Gao and Thompson, Eds., ACS Series 712, Washington 1998.

Best Regards
Isaac

Robert K Szilagyi wrote:

> -= This is automatically added to each message by mailing script =-
> [email-masked] -- To Everybody    |   [email-masked] -- To Admins
> [email-masked] -- HELP CHEMISTRY or HELP SEARCH
> [email-masked] -- archive search    |    Gopher: gopher.ccl.net 70
> Ftp: ftp.ccl.net  |  WWW: http://www.ccl.net/chemistry/   | Jan: [email-masked]

--
Isaac B. Bersuker
Institute for Theoretical Chemistry
Department of Chemistry & Biochemistry
The University of Texas at Austin
Austin, TX 78712, USA
Ph: (512) 471-4671
Fax: (512) 471-8696
Email: [email-masked]