Limits...
R2(2)(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2).

Balasubramani K, Muthiah PT, Lynch DE - Chem Cent J (2007)

Bottom Line: In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist.In both the compounds base pairing also occurs.Thus homo and hetero synthons are present.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Chemistry, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India. bala1679@yahoo.com

ABSTRACT

Background: Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy. Pyrimidine and aminopyrimidine derivatives are biologically important compounds owing to their natural occurrence as components of nucleic acids.

Results: In the crystal structures of two organic salts, namely pyrimethaminium benzenesulfonate monohydrate 1 and 2-amino-4, 6-dimethylpyrimidinium 3-carboxy-4-hydroxy benzenesulfonate dihydrate 2, pyrimethamine (PMN) and 2-amino-4,6-dimethylpyrimidine (AMPY) are protonated at one of the nitrogens in the pyrimidine rings. In both the PMN and AMPY sulfonate complexes, the protonated pyrimidine rings are hydrogen bonded to the sulfonate groups, forming a hydrogen-bonded bimolecular ring motif with graph-set notation R2(2)(8). The sulfonate group mimics the carboxylate anion's mode of association, which is more commonly seen when binding with 2-aminopyrimidines. In compound 1, the PMN moieties are centrosymmetrically paired through a complementary DADA array of hydrogen bonds. In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. Furthermore, this compound is stabilized by intra and intermolecular O-H...O hydrogen bonds.

Conclusion: The crystal structures of pyrimethaminium benzenesulfonate monohydrate and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate have been investigated in detail. In compound 1, the R2(2)(8) motif involving the sulfonate group is present. The role the sulfonic acid group plays in mimicking the carboxylate anions is thus evident. In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. In both the compounds base pairing also occurs. Thus homo and hetero synthons are present.

No MeSH data available.


The schematic diagram for the various hydrogen-bonded motifs observed in compounds                  1 and 2.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2238812&req=5

Figure 1: The schematic diagram for the various hydrogen-bonded motifs observed in compounds 1 and 2.

Mentions: The three dimensional supramolecular architectures in such compounds can be analyzed in terms of various components such as motifs, chains, stacking interactions etc. The schematic representation of the hydrogen-bonded motifs observed in this study is shown in Figure 1. In the crystal structure of compound 1, the asymmetric unit contains a pair of pyrimethaminium (PMN) cations (A and B), benzenesulfonate anions (A and B) and a water molecule as shown in Figure 2. In compound 2, four molecules of 2-amino-4,6-dimethylpyrimidinium (AMPY) cations (A, B, C and D), two molecules of 3-carboxy-4-hydroxy benzenesulfonate (sulfosalicylate) anions (A and B), and two water molecules constitute the asymmetric unit (Figure 3). The PMN moieties are protonated at N1, leading to an enhancement of the internal bond angles at N1 [C2A-N1A-C6A 121.6(2)° and C2B-N1B-C6B 121.5(2)° in compound 1]. The angles are larger than the values observed in neutral pyrimethamine [116.25(18)° (molecule A) and 116.09(18)° (molecule B)] [26]. In compound 2, protonation of the pyrimidine base on the N1 site is reflected in the larger bond angle, as compared with the unprotonated site. The angles at the protonated N1 atom are C2A-N1A-C6A 121.85(17)°; C2B-N1B-C6B 121.93(17)°; C2C-N1C-C6C 121.64(18)° and C2D-N1D-C6D 121.73(18)°. The similar angles at the unprotonated N3 nitrogen are 117.20(17)° (molecule A), 117.52(17)° (molecule B), 117.35(18)° (molecule C) and 117.68(18)° (molecule D). The geometry of the pyrimidine cation agrees with that of other pyrimidine cations reported in the literature [27]. In compound 1, the dihedral angles between the 2,4-diaminopyrimidine and the p-chlorophenyl are 78.50(12)° (molecule A) and 73.20(12)° (molecule B). These values are close to the values observed in the modelling studies carried out on the dihydrofolate reductase-pyrimethamine (DHFR-PMN) complexes [28]. The important torsion angles governing the orientation of the 6-ethyl group are C5A-C6A-C7A-C8A (-105.3(3)° in molecule A) and C5B-C6B-C7B-C8B (110.4 (3)° in molecule B). The lengths of the bonds connecting the pyrimidine and phenyl rings are 1.493(3)Å (molecule A) and 1.496(3)Å (molecule B). These values are in close agreement with those observed in the crystal structure of metoprine (1.495Å in molecule A and 1.478Å in molecule B) [29]. In compounds 1 and 2, the sulfonate group mimics the association of the carboxylate moiety and makes a hydrogen-bonded ring of graph-set notation R22(8) with the PMN and AMPY cations. The hydrogen-bonding geometry of the N-donors to the sulfonate group gave a mean value for the N-H...O hydrogen bond distances involving sulfonates that was slightly longer in range when compared with the carboxylate O atoms indicating that sulfonates form longer and weaker hydrogen bonds with N-donors than carboxylates. These trends are also observed in the present investigation, as indicated in Table 1. The hydrogen bonds formed between the sulfonates and the N-donors were generally linear [30]. In compound 1, the protonated pyrimethaminium (N1A and N1B) cations interact with the (O3A and O2B) oxygen atoms of the sulfonate anions through N-H...O hydrogen bonds (Heterosynthon) forming an eight membered ring motif R22(8) [31-33] (motif II). The pyrimethaminium cations are centrosymmetrically paired through N4-H...N3 hydrogen bonds (Homosynthon) involving the 4-amino group and the N3 atom of the unprotonated pyrimidine to form the ring motif R22(8) (motif III) (Table 1). In addition to the base pairing, one of the sulfonate oxygen atoms (O1B and O1A) (a hydrogen bond acceptor) bridges the 4-amino and the 2-amino groups on both sides of the pairing. The combination of such base-pairing patterns and the further bridging of the bases involved in the pairing by hydrogen bonds, leads to the formation of a linear array of four hydrogen bonds. This is called a complementary DADA array (motif V) of quadruple hydrogen-bonding patterns (D stands for hydrogen-bond donor, and A stands for hydrogen-bond acceptor). The corresponding graph-set notations are R32(8), R22(8) and R32(8) (Figure 4). This type of DADA array of quadruple hydrogen bonds has been observed in some previously reported crystal structures [12].


R2(2)(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2).

Balasubramani K, Muthiah PT, Lynch DE - Chem Cent J (2007)

The schematic diagram for the various hydrogen-bonded motifs observed in compounds                  1 and 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2238812&req=5

Figure 1: The schematic diagram for the various hydrogen-bonded motifs observed in compounds 1 and 2.
Mentions: The three dimensional supramolecular architectures in such compounds can be analyzed in terms of various components such as motifs, chains, stacking interactions etc. The schematic representation of the hydrogen-bonded motifs observed in this study is shown in Figure 1. In the crystal structure of compound 1, the asymmetric unit contains a pair of pyrimethaminium (PMN) cations (A and B), benzenesulfonate anions (A and B) and a water molecule as shown in Figure 2. In compound 2, four molecules of 2-amino-4,6-dimethylpyrimidinium (AMPY) cations (A, B, C and D), two molecules of 3-carboxy-4-hydroxy benzenesulfonate (sulfosalicylate) anions (A and B), and two water molecules constitute the asymmetric unit (Figure 3). The PMN moieties are protonated at N1, leading to an enhancement of the internal bond angles at N1 [C2A-N1A-C6A 121.6(2)° and C2B-N1B-C6B 121.5(2)° in compound 1]. The angles are larger than the values observed in neutral pyrimethamine [116.25(18)° (molecule A) and 116.09(18)° (molecule B)] [26]. In compound 2, protonation of the pyrimidine base on the N1 site is reflected in the larger bond angle, as compared with the unprotonated site. The angles at the protonated N1 atom are C2A-N1A-C6A 121.85(17)°; C2B-N1B-C6B 121.93(17)°; C2C-N1C-C6C 121.64(18)° and C2D-N1D-C6D 121.73(18)°. The similar angles at the unprotonated N3 nitrogen are 117.20(17)° (molecule A), 117.52(17)° (molecule B), 117.35(18)° (molecule C) and 117.68(18)° (molecule D). The geometry of the pyrimidine cation agrees with that of other pyrimidine cations reported in the literature [27]. In compound 1, the dihedral angles between the 2,4-diaminopyrimidine and the p-chlorophenyl are 78.50(12)° (molecule A) and 73.20(12)° (molecule B). These values are close to the values observed in the modelling studies carried out on the dihydrofolate reductase-pyrimethamine (DHFR-PMN) complexes [28]. The important torsion angles governing the orientation of the 6-ethyl group are C5A-C6A-C7A-C8A (-105.3(3)° in molecule A) and C5B-C6B-C7B-C8B (110.4 (3)° in molecule B). The lengths of the bonds connecting the pyrimidine and phenyl rings are 1.493(3)Å (molecule A) and 1.496(3)Å (molecule B). These values are in close agreement with those observed in the crystal structure of metoprine (1.495Å in molecule A and 1.478Å in molecule B) [29]. In compounds 1 and 2, the sulfonate group mimics the association of the carboxylate moiety and makes a hydrogen-bonded ring of graph-set notation R22(8) with the PMN and AMPY cations. The hydrogen-bonding geometry of the N-donors to the sulfonate group gave a mean value for the N-H...O hydrogen bond distances involving sulfonates that was slightly longer in range when compared with the carboxylate O atoms indicating that sulfonates form longer and weaker hydrogen bonds with N-donors than carboxylates. These trends are also observed in the present investigation, as indicated in Table 1. The hydrogen bonds formed between the sulfonates and the N-donors were generally linear [30]. In compound 1, the protonated pyrimethaminium (N1A and N1B) cations interact with the (O3A and O2B) oxygen atoms of the sulfonate anions through N-H...O hydrogen bonds (Heterosynthon) forming an eight membered ring motif R22(8) [31-33] (motif II). The pyrimethaminium cations are centrosymmetrically paired through N4-H...N3 hydrogen bonds (Homosynthon) involving the 4-amino group and the N3 atom of the unprotonated pyrimidine to form the ring motif R22(8) (motif III) (Table 1). In addition to the base pairing, one of the sulfonate oxygen atoms (O1B and O1A) (a hydrogen bond acceptor) bridges the 4-amino and the 2-amino groups on both sides of the pairing. The combination of such base-pairing patterns and the further bridging of the bases involved in the pairing by hydrogen bonds, leads to the formation of a linear array of four hydrogen bonds. This is called a complementary DADA array (motif V) of quadruple hydrogen-bonding patterns (D stands for hydrogen-bond donor, and A stands for hydrogen-bond acceptor). The corresponding graph-set notations are R32(8), R22(8) and R32(8) (Figure 4). This type of DADA array of quadruple hydrogen bonds has been observed in some previously reported crystal structures [12].

Bottom Line: In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist.In both the compounds base pairing also occurs.Thus homo and hetero synthons are present.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Chemistry, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India. bala1679@yahoo.com

ABSTRACT

Background: Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy. Pyrimidine and aminopyrimidine derivatives are biologically important compounds owing to their natural occurrence as components of nucleic acids.

Results: In the crystal structures of two organic salts, namely pyrimethaminium benzenesulfonate monohydrate 1 and 2-amino-4, 6-dimethylpyrimidinium 3-carboxy-4-hydroxy benzenesulfonate dihydrate 2, pyrimethamine (PMN) and 2-amino-4,6-dimethylpyrimidine (AMPY) are protonated at one of the nitrogens in the pyrimidine rings. In both the PMN and AMPY sulfonate complexes, the protonated pyrimidine rings are hydrogen bonded to the sulfonate groups, forming a hydrogen-bonded bimolecular ring motif with graph-set notation R2(2)(8). The sulfonate group mimics the carboxylate anion's mode of association, which is more commonly seen when binding with 2-aminopyrimidines. In compound 1, the PMN moieties are centrosymmetrically paired through a complementary DADA array of hydrogen bonds. In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. Furthermore, this compound is stabilized by intra and intermolecular O-H...O hydrogen bonds.

Conclusion: The crystal structures of pyrimethaminium benzenesulfonate monohydrate and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate have been investigated in detail. In compound 1, the R2(2)(8) motif involving the sulfonate group is present. The role the sulfonic acid group plays in mimicking the carboxylate anions is thus evident. In compound 2, two types of bimolecular cyclic hydrogen bonded R2(2)(8) motifs (one involving the carboxylate group and the other involving sulfonate group) coexist. In both the compounds base pairing also occurs. Thus homo and hetero synthons are present.

No MeSH data available.