Zwitterions - Projects

    Our group has addressed the issue of zwitterion formation both by experimental and theoretical approaches. The experimental studies include ion mobility and hydration work; the theoretical methods include modeling H/D-exchange data and electronic structure calculations.

• From the large body of ion mobility work we carried out on amino acids and small peptides it can be concluded that distinction between zwitterion and charge solvation structures is often not possible on the basis of a cross section experiment. Frequently both the zwitterion and the charge solvation form assume very similar shapes. However, the case of the sodiated oligoglycines is a nice example where zwitterions are much more compact than the corresponding charge solvation structures allowing an unambiguous assignment.[5]
  More about sodiated oligoglycines...

• For smaller systems like cationized amino acids we have systematically studied the effect of cation and amino acid proton affinity on the zwitterion stability by electronic structure calculations supported by ion mobility data.[7] In similar studies we also addressed the effect of charge-dipole alignment and the effect of peptide chain length (self-solvation).[5,8,9] More about these effects on zwitterion stability...

• For the somewhat larger peptides such as bradykinin (9 residues) electronic structure calculations are not feasible. In this case we attempted to approach the problem by theoretically modeling gas-phase H/D-exchange data that had been obtained by others. We developed a simple model to predict the H/D-exchange kinetics for a set of given model structures. Using our bradykinin molecular mechanics structures obtained both for zwitterions and charge solvation structures, we found that a set of low-energy zwitterion structures matched the experimental data far better than a corresponding set of non-zwitterion structures.[14] More about bradykinin...

• Recently, we started a joint project [15] to combine data obtained by H/D-exchange (using D₂O) with results of extensive electronic structure calculations and ion mobility and hydration experiments. This approach is very promising for an in-depth understanding of not only zwitterion stability, but also issues such as the effect of hydration, gas-phase H/D-exchange mechanisms, and peptide shapes, which are in turn believed to be a factor in CID (collision-induced dissociation) and SID (surface-induced dissociation) experiments. This project includes systems of the size of pentapeptides, the arginine-containing systems being the most relevant with respect to the zwitterion question.
  More about arginine-containing pentapeptides...

• Hydration experiments in combination with molecular modeling also provide valuable data for larger peptides of the size of bradykinin. We found that the experimentally determined hydration energies and entropies for adding the first through fourth water molecule to protonated bradykinin (BK) are identical for all four water molecules (ΔH° = -10 kcal/mol, ΔS° = -25 cal/mol/K).[16] BK containing two arginine residues is set up to form a salt bridge structure. In contrast, LHRH, another peptide of similar mass, contains only one arginine and no acidic site at all. The (LHRH)H⁺ hydration enthalpy and entropy values are very different from those of BK with larger values for the first water molecule (ΔH° = -13 kcal/mol, ΔS° = -36 cal/mol/K) and systematically decreasing values for the second (-10, -27), third (-9, -21), and fourth (-9, -21) water molecule. Molecular modeling simulations show markedly different solvation behavior. In (BK)H⁺ the water molecules form a water chain connecting the deprotonated C-terminus with one of the protonated arginine side chains. In
  (LHRH)H⁺ the water molecules more evenly solvate the entire peptide surface including the protonated arginine side chain.
  More about bradykinin...