Supramolecular Structures and Tautomerism of Carboxylate Salts of Adenine and Pharmaceutically Relevant N⁶-Substituted Adenine

Abstract

Co-crystal and salt formation of the kinetin analogue N 6 -benzyladenine with the pharmaceutically acceptable co-crystal and salt formers maleic acid, oxalic acid, glutaric acid, succinic acid, benzoic acid and fumaric acid has been studied by solid-state and solvent-drop grinding in combination with X-ray powder diffraction. In all cases salt or co-crystal formation was observed. Single crystals of (bzadeH + )(mal -) (1) and (bzadeH + )2(ox 2-) (2) were obtained by solution crystallization and the X-ray structures are reported along with that of (adeH + )2(mal -)2 . ade . 2H2O (3) (bzadeH + = N 6 -benzyladeninium, adeH + = adeninium, ade = adenine, mal -= hydrogen maleate, ox 2-= oxalate). The hydrogen-bonding motifs in 1 -3 are discussed. The salts contain a robust bzadeH + -carboxylate or ade-carboxylate R2 2 (9) heterosynthon involving the protonated Hoogsteen sites (N6-H, N7-H) of bzadeH + and ade. Molecular recognition between the protonated Hoogsteen site and the carboxylate group stabilizes the unusual 7H,9H tautomer of bzadeH + in 2 and the non-canonical 7H-adenine tautomer in 3.* To whom correspondence should be addressed. ABSTRACT Co-crystal and salt formation of the kinetin analogue N 6 -benzyladenine with the pharmaceutically acceptable co-crystal and salt formers maleic acid, oxalic acid, glutaric acid, succinic acid, benzoic acid and fumaric acid has been studied by solid-state and solvent-drop grinding in combination with X-ray powder diffraction. In all cases salt or co-crystal formation was observed. Single crystals of (bzadeH + )(mal -) (1) and (bzadeH + )2(ox 2-) (2) were obtained by solution crystallization and the X-ray structures are reported along with that of (adeH + )2(mal -)2 . ade . 2H2O (3) (bzadeH + = N 6 -benzyladeninium, adeH + = adeninium, ade = adenine, mal -= hydrogen maleate, ox 2-= oxalate). The hydrogen-bonding motifs in 1 -3 are discussed. The salts contain a robust bzadeH + -carboxylate or ade-carboxylate R2 2 (9) heterosynthon involving the protonated Hoogsteen sites (N6-H, N7-H) of bzadeH + and ade. Molecular recognition between the protonated Hoogsteen site and the carboxylate group stabilizes the unusual 7H,9H tautomer of bzadeH + in 2 and the non-canonical 7H-adenine tautomer in 3.3

Role of Achiral Nucleobases in Multicomponent Chiral Self‐Assembly: Purine‐Triggered Helix and Chirality Transfer

“…This d-spacing is larger than one molecular length of Fmoc-Glu (1.34 nm) but shorter than two,indicating abilayer structure of Fmoc-Glu with an overlapping Fmoc moiety.Itwas found that the XRD patterns do not change significantly after assembly with the nucleobase.I nc ontrast, we changed the mixing ratio of Fmoc-Glu to Aa nd investigated their gel formation ( Figure S1), nanostructures ( Figure S10), and CD spectra ( Figure S11), and found that only in the ratio of 2:1, Fmoc-Glu and Af ormed the stable hydrogel and uniform helical fibers.B ased on these results,w es peculate that the nucleobase laterally attached on the bilayer surface of Fmoc-Glu (Figure 4b). Thepurine bases interact with two alternate glutamic acids through hydrogen bonding [17] (Figure 4b, inset), and the bulky purine base may cause the torsion of neighboring Fmoc-Glu molecules.T his purine-base-inserted bilayer structure serves as ab asic repeat unit, which forms multiple bilayers,a nd further hierarchically self-assembles into higher level nanohelices.The larger conjugated structure of purine nucleobases than that of pyrimidines is attributed to stronger p-p stacking, causing the formation of hydrogels and chiral structures.After inserting ThT, the d-spacing is aslightly enlarged (2.72 nm), and the increment (0.32 nm) may be ascribed to the length of the dimethylbenzenamine moiety. Thebenzothiazole moiety is inserted into the bilayer to cause the helical pitch to increase further (Figure 4c).…”

Molecular recognition of an adenine derivative by organoplatinum(II) complexes with hydrogen-bonding functionality

“…The interest of these systems is aimed at better understanding the intermolecular interactions that are involved in these diverse molecular bio-recognition processes, and to provide tools to aid in the design of efficient tailor-made probes and drugs that could be potentially applied in number of theranostic applications [3,4]. Hydrogen bonding interactions are a major driving force in the formation of numerous supramolecular structures involving nucleobases with a variety of structural geometries [5]. Indeed, natural and artificial host-guest complexes as well as many nucleic acid structural elements are a direct result of specific, highly-directional intermolecular hydrogen bonding interactions [5,6].…”

“…Hydrogen bonding interactions are a major driving force in the formation of numerous supramolecular structures involving nucleobases with a variety of structural geometries [5]. Indeed, natural and artificial host-guest complexes as well as many nucleic acid structural elements are a direct result of specific, highly-directional intermolecular hydrogen bonding interactions [5,6].…”

Synthesis and Experimental Studies on Supramolecular Synthons of Aminoguanidinium Carboxylates: A Case Study of π‐HoleBonded Carbon Bonding via Theoretical Approaches

“…On the other hand, among the dicarboxylates namely maleate anion ( Figure b ) is a key molecule in crystal engineering due to its structural aspects in terms of deprotonation, inter and intramolecular hydrogenbonding functionality and flexible conformational features . Maleate anions were used to complex with different organic components; base molecules, amino acids as well as drug molecules (e. g., quinolone 4‐carbaldoxime, L‐methionine, Adenine, clofazimine, lamivudine, caffine, aminopyridinium, guanidinium, umifenovir, medendazole, tetrathiafulvalene etc.,) and generate polymorphism, salts, solvates, co‐crystals with interesting ring motifs and analyzed their pharmaceutical properties and semiconducting properties . In addition investigations in solution state regarding their solubility or their kinetic stabilities or theoretical studies on proton‐tautamerism 53 and energy parameters are also performed .…”