Conformational properties of a zwitterion in water solution
3-chloro-GABA is a derivative of the neurotransmitter GABA in the mammalian nervous system. GABA is techniqually an amino acid although never found in proteins. Like other free amino acids it's actually a zwitterion in aqueous solution. Zwitterions are thought not to be stable in the gas phase or the vacuum.
Modelling zwitterions thus usually requires some representation of the solvent. In this exercise this is performed using the continuum solvation model COSMO that models the solvent as a dielectric medium characterized by a dielectric constant. Continuum solvation models are often necessary to give some minimal description of solvation effects. They are, however, crude models that can not give describe e.g. solvent-solute hydrogen-bonding effects well.
1. What happens when you run a normal gas geometry optimization using the semiempirical method AM1 on zwitterionic 3-chloro-GABA using these starting coordinates? :
! AM1 OPT
*xyz 0 1
O -2.740958000 -0.111916000 0.184531000
C -1.525946000 0.136971000 0.022372000
O -1.071676000 1.224690000 0.496340000
C -0.627746000 -0.844200000 -0.738440000
C 0.783627000 -1.029800000 -0.161378000
C 1.784155000 0.054984000 -0.625051000
N 2.143421769 -0.063809934 -2.081322397
H -1.120739000 -1.835785000 -0.770944000
H -0.554151000 -0.512921000 -1.792668000
Cl 0.756972000 -1.097187000 1.203488000
H 1.185234000 -2.014329000 -0.496253000
H 1.363889717 1.064471227 -0.419940839
H 2.699248486 -0.019328715 0.003079285
H 2.972661617 0.460920039 -2.264727389
H 1.391472120 0.293924384 -2.634511816
H 2.286448661 -1.059933614 -2.308365093
*
2. What happens if we include the COSMO solvation model?
Inputline becomes:
! AM1 OPT COSMO(Water)
3. For a flexible molecule like 3-Cl-GABA there must be multiple conformers, i.e. multiple local minima.
Locate as many different conformers as you can (or have patience for). Use AM1 and COSMO together, part 2 above. Which one is the lowest in energy (the global minimum)? Why do you think this conformer is more stable than the others (i.e. using your chemical intuition what would it make it more stable)? Can you think of a way to experimentally confirm which conformer is present in real aqueous solution?
The report should show pictures of the located conformers (only optimized geometries) and either table or graph of relative conformational energies.