Alanine
The ground state optimization energy of the neutral, protonated and deprotonoted Ala
calculated at B3LYP/6-311++G(d,P) level of theory in aqueous medium is lowered by 14.28,
74.02 and 62.84 Kcal/mol, respectively compared their gas phase value. However, the ground
state optimization energy of neutral, protonated and depronoted Ala calculated at HF/6311++G(d,p) level is found to be lowered by 14.79, 72.50 and 69.21 Kcal/mol, respectively. The
effect of solvation on optimization energy of protonated and deprotonated form of the Ala
molecule is more pronounced compared to its neutral form. we would like to discuss about the
bond lengths associated to the –COOH and –NH2 functional groups of the Ala molecule because
the protonation and deprotonation process occur at these two functional group and therefore a
change is expected in the structural parameters associated to
–COOH and –NH2 functional
groups. The bond lengths C1 = O3, C1 – O2, C1 – C4, C4 – N9 and N9 – H11 of neutral Ala
calculated at B3LYP/6-311++G(d) level of theory in gas phase is 1.2055, 1.3527, 1.5187, 1.4592
and 1.0140 Å, respectively. Upon protonation the bond lengths, C1 = O3, C1 – C4, C4 – N9 and N9
– H11 increased by 0.0011, 0.0255, 0.0291 and 0.0076 Å, respectively. However, the bond length
C1 – O2, where hydrogen atom was directly attached, decreases by 0.0324 Å. A similar kind of
trend in change of bond length has been also observed upon deprotonaion of the molecule.
Further, the bond lengths C1 = O3, C1 – O2, C1 – C4, C4 – N9 and N9 – H11 of neutral Ala in
aqueous medium is 1.2140, 1.3398, 1.5203, 1.4634 and 1.0210 Å, respectively. Moreover, a
similar kind of pattern has been observed for the change in bond lengths of Ala on protonation
and deprotonation as we have seen in case of gas phase. The -C=O bond lengths of Ala
calculated at B3LYP/6-311++G(d) and HF/6-311++G(d) level of theories are 1.2055Å and
1.1945 Å , respectively which are in the good agreement of the experimental value, 1.19 Å [30].
The N9C1 C4 and C4C1O3 is 108.10 and 125.20 and 108.40 and 1250 calculated at both,
B3LYP and HF methods, respectively. The calculated values of N9C1 C4 and C4C1O3 are in
good agreement with the experimentally calculated values 110.00 and 125.60, respectively [34].
The structure of protonoted and deprotonoted Ala is given in Fig. 2(A). In the protonated form
of Ala, the N9C1 C4 and C4C1O3 is 104.30 and 121.70 and 105.40 and 121.60 calculated at
DFT and HF methods, respectively. The value of N9C1 C4 increases at both the level of
theories. In case of the deprotonated Ala, the N9C1C4 and C4C1O3 is 113.70 and 115.60, and
1140 and 115.80 calculated at DFT and HF methods, respectively.
Glycine
The ground state optimization energy of the neutral, protonated and deprotonoted Gly
calculated at B3LYP (HF) / 6-311++G(d,p) level of theory in aqueous medium was found be
lowered by 14.56 (15.16), 77.47 (78.66) and 68.07 (72.28) Kcal/mol, respectively compared to
their the gas phase optimization energy. The bond length C1 = O3 is 1.205Å and 1.183 Å
calculated at B3LYP and HF methods, respectively. Thus the bond length is well supported by
the experimental value, 1.205 Å [30]. The C4C1O3 is 125.30 and 125.30 and N9C1C4 is 110.50
and 110.30 calculated at DFT and HF, respectively along with the experimental values, 125.50
and 112.10[30]. The protonated Gly, where the –H atom is attached through the amino group,
form a hydrogen bond with –O atom of the –C=O group. The lengths of the hydrogen bond are
calculated to be 1.953 Å and 2.52 Å at DFT and HF level of theories, respectively. We can see
that in the protonated form of the Gly, the C4C1O3 decrease by 30 to 40 than that of the neutral
form of the Gly. Before calculating the pKa values of the amino acids, we must need to know the
value of gas phase acidity. The gas phase free energies of the Gly and their conjugate bases were
calculated from their optimized gas phase geometries.
Phenylalanine
The ground state optimization energy of the neutral, protonated and deprotonoted Phe
calculated at B3LYP (HF) / 6-311++G(d,p) level of theory in aqueous medium was found be
lowered by 17.78 (17.62), 120.95 (70.92) and 102.11 (69.61) Kcal/mol, respectively compared to
their the gas phase optimization energy. It is to be noted that the change in optimization energy
of protonated and deprotonated Gly is quite significant in going from gas to aqueous medium
relative to the neutral Phe. The C=O bond length is not affected much upon protonation or
deprotonation of the neutral Phe molecule. In gas phase, the N1C3C6 is 108.70 and 110.80 for
the neutral and in protonated form it decreases to 103.90 and 106.10 at B3LYP and HF methods,
respectively. The decrease in bond angle on protonation of the Phe molecule can be explained in
terms of the formation of the hydrogen bonds of length, r=2.06 between –H atom of the amino
group and –O atom of the –COOH group. The strength of hydrogen bonds becomes weaker in
case of HF method of calculations.
Tyrosine
In this molecule the protonation can takes place at both the functional groups, –COOH
and –OH. Thus, we have two deprotonation states compared to other three molecules discussed
above. The optimization energy of the neutral, protonated and deprotonoted Tyr calculated at
B3LYP (HF)/6-311++G(d,p) level of theory in aqueous medium shows a decrease of 23.66
(25.52), 81.15 (88.07), 74.11 (79.44) and 71.19 (74.62) Kcal/mol, respectively compared to that
of the gas phase optimization energy. By looking at the optimization energy of two protonated
structures of Tyr, it seems that the structure where the –H atom is detaching from –OH group
upon deprotonation is more stable than that of the other deprotonated structure. The carboxylate
has a COOH…H2N hydrogen bond, but no such interaction was observed with the hydroxyl
group because of the rigidity of the aromatic ring. A similar kind of effect can be seen to the
phenoxide conformation and neutral tyrosine. But in the phenoxide conformation there is a very
weak hydrogen bond interaction between –O atom of the –COOH group and –H atom of the
benzene ring. This arises because the excess charge on the phenoxide ring, which is partially
delocalized to the para carbon of the aromatic ring. While in the protonated form, a strong
hydrogen bond (r=2.06Å) between the –H atom of the amine group and –O atom of the –COOH
group has been also observed.