lunedì 18 luglio 2016


Consideraimo ora anche la stereoisomeria delle conformazioni, che sono arrangiamenti delle posizioni tridimensionali dei vari gruppi di una molecola ottenuti PER ROTAZIONE INTERNA intorno ai legami singoli. Anche dei conformeri bisogna tenere conto per le varie simmetrie. Per esempio, consideriamo il 2,3 butan diolo:

Ecco le sue proiezioni di Newman:

Si nota che la presenza percentuale dei conformeri è diversa. 

Research Projects


Conformational Analysis

Structure leads to function.  This is true, not only througout biology, but in chemistry as well.  The macroscale function of a molecule is directly tied to the atomic scale structure that molecule adopts.  The function of a complexly folded protein, or the physical properties of a simple water molecule are quick examples.  For a molecule with intramolecular rotational freedom, there are an infinite number of structures, or conformations, it may adopt.  Are there preferred conformations?  If so, what are they?  And what drives the molecule to adopt these conformations?  These are the questions we try to answer.
To fully appreciate the purpose of this project, it is necessary that you first understand the chemist's visual perspective of molecules and molecular rotation.  Below are two representations of meso-2,3-butanediol.




The first picture uses the wedge (coming out) and dash (going in) notation to present a three-dimensional perspective.  The animation clearly shows the 3-D structure of the molecule.  This molecule can adopt many conformations via rotation about each bond, but we are primarily concerned with rotation about the C2-C3 bond.  This particular rotation is represented by each of the three images below.

(showing your eye's perspective and the bond to rotate)

(a side-angled perspective of the rotation)

(a classic Newman projection perspective)

The previous animations are quite simple representations of intramolecular rotation.  In reality, the molecule is twisting and bending, back and forth in all directions, with respect to each bond.  The animation to the right presents a slightly more realistic picture of molecular rotation, although we are still focusing only on the C2-C3 bond.  As the C2-C3 bond rotates, the molecule will experience conformations of high energy, and conformations of low energy.  It is logical that the molecule will prefer to exist in conformations of low energy.  How can we experimentally determine which conformations are low energy and preferred?  The answer, as is often the case, is NMR!
A nuclear magnetic resonance (NMR) spectrum of our compound can give us conformational information.  The coupling constant between the vicinal protons A and B is directly related to their dihedral angle, which is directly related to the rotational conformation of the molecule.

acquire NMR spectrum

1H NMR spectrum of protons
A and B in CD3OD at 50 °C
reproduce the NMR spectrum in a computer program to extract the coupling constant
computer simulated NMR spectrum
(JA-B = 5.1 Hz)


In the absence of any conformational influence, each low energy rotamer shown to the left would comprise 33%.  The results show the first rotamer is slightly favored.  Why?  For the typical Organic Chemistry student, the answer is the steric repulsion of the vicinal methyl groups.  While that may be true in this case, there are many other possible explanations.  Steric bulk is not the be-all and end-all.  Other conformational influences may include:
  1. coulombic repulsion of the electronegative oxygen atoms and their lone pair electrons.
  2. potential intramolecular hydrogen bonding between the vicinal hydroxyl groups.
  3. potential intermolecular hydrogen bonding between the molecule and the solvent.
  4. the polarity of the conformer and the polarity of the solvent in which it is dissolved.
  5. hyperconjugation among vicinal sigma-bonding and sigma*-antibonding orbitals.
Why is any of this important?  The conformational influences that dictate the structure of small molecules like that shown above, are the same influences which affect larger molecules like proteins.  Small molecules are easier to analyze than proteins, and serve as nice model systems.  If we can understand why a small molecule adopts the structure it does, we can understand better why a protein chain twists and folds the way it does.  A deeper understanding of conformational structure provides chemists the information needed to choose a better solvent to achieve higher reaction yields, or perhaps build a better, more effective drug.  The implications and applications of the knowledge gained from comformational analysis are broad and far-reaching across the scientific community.

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