*3.1.5. Quantum chemical analysis of the electron and geometric structures of hydrogen bonds in complementary pairs of NA bases and polysaccharides by Ab initio calculations in the 6-31G\* basis*

Let us optimize the geometry of the above complexes by *ab initio* calculations in the 6-31G\* basis (Table 6).


Note: Energy (kcal/mol) was obtained by *аb initio* calculations in the 6-31G\* basis.

**Table 6.** Energy of hydrogen bonds between the nucleotides T, A, C, and G and the carboxyl group of glucuronic acid

In general, *аb initio* calculations confirmed the results obtained by the PM3 method and described in the previous section. The interaction of the carboxyl group of glucuronic acid and the nucleotides is possible, and its energy is sufficient for hydrogen bonding similar to that in the classical complementary DNA pairs. However, the energy of interaction changes with nucleotide in another order: the interaction with the carboxyl group of glucuronic acid is more advantageous with C and G and less advantageous with T and A (Table 6). As for the interaction of the hydroxymethyl group of N-acetylglucosamine with NA bases, the results differed from those obtained by the PM3 method. If the two fragments were initially bonded by one hydrogen bond, like in the case of the interaction between the carboxymethyl group and hydrogen of a base (Fig. 8), then, during optimization, the groups were rotated relative to each other so that the interaction involved the atoms of the monosaccharide ring that by no means can bind to the nucleotide. This is probably explained by the fact that *аb initio* calculations yield higher estimates of hydrogen bond energy as compared with the PM3 method. As a result, greater energy estimates are obtained for the interactions of H with distant O and N and the atoms are brought close together during optimization to form new hydrogen bonds, which are impossible in the double helix.

Thus, *аb initio* calculations in the 6-31G\* basis confirmed that the carboxyl group of glucuronic acid is capable of hydrogen bonding to the bases T, A, G, and C; the two bonds formed in each case are similar to those occurring in the complementary pairs AT and GC.

*3.1.6. PM3 Analysis of the electron and geometric structures of hydrogen bonds in complementary pairs of a NA–glucuronic acid double helix. Selectivity in template synthesis of polysaccharides* 

276 The Complex World of Polysaccharides

follows.

*the 6-31G\* basis* 

basis (Table 6).

glucuronic acid

Carboxyl group of

bases with N-acetylglucosamine with various initial arrangements of the interacting groups yielded complexes with one or two hydrogen bonds. Complexes containing one hydrogen bond were most advantageous in terms of energy according to PM3 computations. The nucleotides proved to vary in energy of interaction with the hydroxymethyl group: the interaction was more efficient with T and C than with G and A. The conclusions are as

1. Quantum chemical computations showed that NA bases and the carboxyl or hydroxymethyl group of sugars are capable of forming hydrogen bonds, which are comparable in energy with those occurring in the complementary AT and GC pairs. 2. The bonds are nonequivalent. The carboxyl group forms tighter bonds with purines and less tight bonds with pyrimidines. In contrast, the hydroxymethyl group forms more

3. The differences in energy computed for hydrogen bonds are insufficient for selection of

Let us optimize the geometry of the above complexes by *ab initio* calculations in the 6-31G\*

glucuronic acid -12.95 -13.77 -15.98 -17.89

**Table 6.** Energy of hydrogen bonds between the nucleotides T, A, C, and G and the carboxyl group of

In general, *аb initio* calculations confirmed the results obtained by the PM3 method and described in the previous section. The interaction of the carboxyl group of glucuronic acid and the nucleotides is possible, and its energy is sufficient for hydrogen bonding similar to that in the classical complementary DNA pairs. However, the energy of interaction changes with nucleotide in another order: the interaction with the carboxyl group of glucuronic acid is more advantageous with C and G and less advantageous with T and A (Table 6). As for the interaction of the hydroxymethyl group of N-acetylglucosamine with NA bases, the results differed from those obtained by the PM3 method. If the two fragments were initially bonded by one hydrogen bond, like in the case of the interaction between the carboxymethyl group and hydrogen of a base (Fig. 8), then, during optimization, the groups were rotated relative to each other so that the interaction involved the atoms of the monosaccharide ring that by no means can bind to the nucleotide. This is probably explained by the fact that *аb initio* calculations yield higher estimates of hydrogen bond energy as compared with the PM3 method. As a result, greater energy estimates are obtained for the interactions of H

**Т А C G** 

stable hydrogen bonds with pyrimidines and less stable bonds with purines.

*3.1.5. Quantum chemical analysis of the electron and geometric structures of hydrogen bonds in complementary pairs of NA bases and polysaccharides by Ab initio calculations in* 

monosaccharides with necessary structures.

Note: Energy (kcal/mol) was obtained by *аb initio* calculations in the 6-31G\* basis.

Consider the possibility of polysaccharide synthesis on single-stranded NA. It is clear that, even if some hydrogen bonds are formed between NA bases and monosaccharides, such bonds are not necessarily formed in a polysaccharide–NA double helix because of geometric limitations.

Let us construct two oligomers each consisting of five monomeric units: NA (GCGCA) and oligosaccharide (a HA fragment). As NA, we use the chain analyzed above (Fig. 6). Constructing a chain of five HA monosaccharides, let us rotate the units around the bonds between them so that the carboxyl and hydroxymethyl groups of the resulting chain can be hydrogen bonded to nucleotides. Let us bring the two chains close together so that the distance between groups was 1.5-2.5 Å as in Figs. 9 and 10, with G and A interacting with the carboxyl group (Fig. 9) and C, with the hydroxymethyl group (Fig. 10). Let us fully optimize the resulting double helix by the PM3 method. The energy of hydrogen bonding in the resulting construct (Figs. 9, 10) is -7.04 kcal/mol, rather high and almost reaching the energy of interaction in the classical DNA double helix (-8.82 kcal/mol, Fig. 6).

Е = -7.04 kcal/mol per complementary pair

**Figure 9.** Hydrogen bonding in the complementary pairs G–glucuronic acid, A–glucuronic acid, and C– N-acetylglucosamine in a DNA–polysaccharide double helix exemplified by a five-unit chain. Quantum chemical computation by the PM3 method.

Е = -7.04 kcal/mol per complementary pair

**Figure 10.** Hydrogen bonding in the complementary pairs G–glucuronic acid, A–glucuronic acid, and C–N-acetylglucosamine in a DNA–polysaccharide double helix exemplified by a five-unit chain. Quantum chemical computation by the PM3 method. (Another view point).

The interaction purine–glucuronic acid in the NA–polysaccharide double helix was much the same as in isolation: the lengths of the two hydrogen bonds were 1.79 Å. However, interesting differences were observed for the pyrimidine–N-acetylglucosamine interaction in the double helix and in isolation. In addition to the only hydrogen bond (1.86 Å) formed in isolation (Fig. 10), another hydrogen bond (1.84 Å) was formed with O of the neighboring nucleotide in the double helix. Moreover, there was one more, weaker hydrogen bond (2.59 Å) directed oppositely. Thus, N-acetylglucosamine also forms two hydrogen bonds with nucleotides of an NA strand, which ensures its sufficiently tight and highly selective interaction with nucleotides of a native NA molecule. In addition, computations were performed for incorrect sequences of monosaccharides. As in the case of incorrect sequences of bases in the DNA double helix, low-energy hydrogen bonds were obtained in this variant or the NA–polysaccharide double helix was not formed at all because the bonds were disadvantageous in terms of energy. The conclusions are as follows.

