Enhanced Stabilization of G‐Quadruplex DNA by [Ni₄L₆]⁸⁺ Cages with Large Rigid Aromatic Ligands

Abstract

Two tetrahedral nickel(II) cages, [Ni 4 L 6 ] 8+ (1 and 2), with large rigid aromatic ligands were synthesized, and their Gquadruplex DNA binding abilities were investigated. The crystal structure of cage 1 confirmed its tetrahedral [Ni 4 (L1) 6 ] 8+ [L1 = 4,4′-bis(2-pyridylimine)biphenyl] formulation. The nickel centers have N 6 coordination environments with distorted octahedral geometries, and the average Ni-Ni bond length is 12.89 Å. It is exciting that cages 1 and 2 showed effective stabilization of antiparallel G-quadruplex DNA (ΔT m = 39.09-40.90°C). Subsequent G-quadruplex binding studies with analogous cages (3-6) were performed to explore the impact of the central metal ion and the overall charge on the interaction with G-quadruplex DNA. The corresponding iron(II) cages [Fe 4 (L1) 6 ] 8+ (3) and [a] 3540 FRET melting except that different concentrations of duplex DNA ds26 were added. The final analysis of the data was performed with the Origin 7.5 software (Origin Lab Corp.).

Programmable synthesis of well-defined, glycosylated iron(ii) supramolecular assemblies with multivalent protein-binding capabilities

“…46 With these considerations in mind, we initially selected benzidinedisulfonate as a polar, charged ditopic amine subcomponent that has been shown to form tetrahedral assemblies in aqueous solution. [47][48][49] Accordingly, treatment of glucose-substituted subcomponent A with commercial benzidinedisulfonic acid and Fe(BF 4 ) 2 •6H 2 O in the presence of [NMe 4 ][OH] in water (Scheme 1) resulted in the formation of one major species as assayed by 1 H NMR spectroscopy. Notably, these reaction conditions were optimized to include an excess of hydroxide ion, which was used to both deprotonate benzidinedisulfonic acid, and to achieve de-O-acetylation of acetate-protected subcomponent A in-situ.…”

Diastereomer Resolution of M4L6 Coordination Cages by Ultra‐High‐Resolution Ion‐Mobility Mass Spectrometry

“…To explore the effects of varying the metal ion, [Co‐ 1 ](X) 8 (X=ClO 4 − , BF 4 − ) and [Ni‐ 1 ](ClO 4 ) 8 [11] were prepared. The 1 H NMR of [Co‐ 1 ](X) 8 (Figures S4, S5) confirmed the presence of the desired tetrahedral cages and proved sufficient to determine the relative ratio of S 4 ‐, C 3 ‐ and T ‐symmetric diastereomers in solution (Table 1).…”

“…[9] The resulting increase in resolving power has facilitated the separation of species with closely related structures, for example diastereomeric dimers of thalidomide revealing quantitative enantiomeric compositions. [10] Here we employ cIM-MS to resolve and probe the stability of interconverting M 4 L 6 (M = Fe 2 + , [5] Co 2 + or Ni 2 + , [11] M-1) cage diastereomers (T, S 4 and C 3 ), that differ only in ligand geometries (Figure 1b, blue = anti linkage, yellow = syn linkage) brought about through differences in axial chirality at the metal ions (Figure 1b, grey/teal). Notably, cIM-MS is not limited to diamagnetic metals, and thus was applied to high-spin octahedral Ni 2 + complexes, known for their long electronic relaxation times [12] that limit characterisation by 1 H nuclear magnetic resonance (NMR) spectroscopy.…”

Interaction of Metal Complexes with G‐Quadruplexes

“…The methylene group connecting the phenyl moieties was suppressed, hence rigidifying the ligand. 114 A tetrahedral cage of formula [Ni II 4 L 6 ] 8+ was obtained, whose dimensions are 21 and 7 Å (length and diameter of the six edges, respectively, 110). Notably, the metal ion retains its octahedral geometry, similarly to the cylinders, but herein occupies the apexes.…”