Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular structures

Abstract

Supramolecular self-assembly is not only one of the chemical roots of biological structure but is also drawing attention in different industrial fields. Here we study the mechanism of the formation of a complex flower-shaped supramolecular structure of pyrimido[4,5-d]pyrimidine nucleosides by dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, nuclear magnetic resonance and X-ray analysis. Upon removing the hydroxyl group of sugars, different flower-shaped superstructures can be produced. These works demonstrate that complex self-assembly can indeed be attained through hierarchical non-covalent interactions of single molecules. Furthermore, chimerical structures built from molecular recognition by these monomers indicate their potential in other fields if combined with other chemical entities.

Figure 1. SEM images and molecular structures of compounds 1 and 2.

(a) Flower-shaped superstructure self-assembled by 1 in water (0.2 mg ml⁻¹) and its molecular structure with the systematic numbering. (b) Microsphere superstructure self-assembled by 2 in water (0.2 mg ml⁻¹) and its molecular structure showing the two-faced hydrogen bond acceptor–donor motif of adenine and thymine: the arrows of A at A represent the hydrogen acceptors and the arrows at D represent the hydrogen donors. Scale bars, (a) 10 μm; (b) 5 μm.

Figure 2. SEM images showing the formation process of the flower-shaped superstructure.

(a–g) Intermediates of incomplete microflowers were observed within 14 h, which was in a quite similar manner mimicking the natural flowers blooming from buds. (h,i) only the fully unfolded microflowers were observed after 14 h (h, backside; i, frontside). Scale bars, (a–c) 5 μm; (d–i) 10 μm.

Figure 3. Structures of two monomeric conformers and the base pair motifs between them.

(a) Conformer A adopts an anti conformation with an N-type (3′-endo) sugar puckering and 5′-OH at ap position. (b) Conformer B adopts high-anti conformation with an S-type (3′-exo) sugar puckering and 5′-OH at sc position. The intramolecular H-bond between 2′-OH and N1B is shown in green colour. (c) Two possible base pair motifs of compound 1. (d) A detailed view of the reverse Watson–Crick base pairs in the solid state of 1. The repeated hydrogen bonds unit connecting conformers A and B together in the whole assembly is highlighted in green colour. Atoms are coded as follows: red, oxygen; blue, nitrogen; gray, carbon; white, hydrogen.

Figure 4. Complicated hydrogen bond networks of compound 1.

(a) The overall multilayered supramolecular structure of compound 1. (b) The interactions between conformers A and B (viewed through z direction of a). The base moieties of adjacent layers are not stacked and the covalent bonds of different layers are displayed in yellow or purple colour, respectively. (c) The interactions between conformer A and A (viewed through −x direction of a). (d) The interactions between conformer B and B (viewed through x direction of a). The total repeated 20 hydrogen bonds unit crossing different layers of the whole assembly is highlighted in green colour. Atoms are coded as follows: red, oxygen; blue, nitrogen; gray, carbon; white, hydrogen.

Figure 5. SEM images of compounds 3–4 and the single-crystal structure of compound 4.

(a) Spiral flower-shaped superstructure formed by 3 in water (0.2 mg ml⁻¹). (b) Ball flower-shaped superstructure formed by 4 in water (0.2 mg ml⁻¹). (c) The single-crystal structure of 4. The repeated unit of 13 intra and intermolecular hydrogen bonds is highlighted in green colour. Atoms are coded as follows: red, oxygen; blue, nitrogen; gray, carbon; white, hydrogen. Scale bars, (a,b) 10 μm.

Figure 6. Chimeric morphologies formed by mixing J-AT with other nucleosides.

(a) J-AT:Adenosine (1:1 mole ratio). (b) J-AT:Uridine (1:1 mole ratio). (c) J-AT:Uridine (1:5 mole ratio). (d) J-AT:Cytidine (1:1 mole ratio). (e) J-AT:Cytidine (1:5 mole ratio). (f) J-AT:Guanosine (1:1 mole ratio). (g) J-AT:Guanosine (1:5 mole ratio). (h) J-AT:compound 2 (1:1 mole ratio). (i) J-AT:J-TA (1:1 mole ratio). Scale bars, (a,g–i), 5 μm; (b–f), 10 μm.