Minimal nucleotide duplex formation in water through enclathration in self-assembled hosts

Abstract

Short nucleotide fragments such as mono- and dinucleotides are generally unable to form stable hydrogen-bonded base pairs or duplexes in water. Within the hydrophobic pockets of enzymes, however, even short fragments form stable duplexes to transmit genetic information. Here, we demonstrate the efficient formation of hydrogen-bonded base pairs from mononucleotides in water through enclathration in the hydrophobic cavities of self-assembled cages. Crystallographic studies and 1H- and 15N-NMR spectroscopy clearly reveals pair-selective recognition of mononucleotides and the selective formation of an anti-Hoogsteen-type base pair in the cage's cavity. Within an analogous expanded cage, dinucleotides are also found to form a stable duplex in water. These results emphasize how hydrogen-bonded base pairing is amplified in a local hydrophobic area isolated from aqueous solution.

Trinucleotide duplex formation inside a confined nanospace under supercooled conditions

“…One recently successful approach has involved the use of hydrophobic cavities in pyrazine-pillared coordination cages dispersed in water 3 . Hydrogen-bonded base pairing in a hydrophobic cavity isolated from the water phase has been proposed to be responsible for the stabilization of anti-Hoogsteen-type base pairs of minimal (mono-and di-) nucleotides.…”

Dispersions based on noble metal nanoparticles-DNA conjugates

“…Fujita et al have described the consequences of using watersoluble synthetic hosts to coax mono-and dinucleotides into similar behavior [23]. Using a basic palette of square-planar metal centers to provide 90°'corners' and relatively simple multidentate N-donor ligands as 'molecular panels', they have produced an array of discrete two-dimensional (2D) and three-dimensional (3D) structures including macrocycles and capsules [24].…”

Encapsulation of Reactive Intermediates

“…In a cage, only one pair of nucleotide is necessary to achieve a selective binding as demonstrated by the formation of a hydrogen -bonded aggregate between 5 ′ -adenosine monophosphate 24 and 5 ′ -uridine monophosphate 25 resulting in the preferred formation of complex 24.25 @ 23 over ( 24 ) 2 @ 23 and ( 25 ) 2 @ 23 (Scheme 10.8 ). 15 This selectivity is due to the fact that the nucleobases cannot effi ciently form hydrogen bridges with themselves. The pillared cage 23 is an appropriate host because it possesses a fl at hydrophobic pocket perfectly suited for the binding of planar aromatic guests as a result of an ideal interplanary distance between the panels (6.6 Å ).…”