3-Substituted xanthines as promising candidates for quadruplex formation: computational, synthetic and analytical studies

Abstract

Our computational studies suggest that 3-substituted xanthines are good candidates for tetrad and quadruplex structures. 3-Methylxanthine (3MX) has been synthesized from 7-benzylxanthine, and the existence of tetrameric and octameric aggregates of 3MX with NH 4 + , Na + and K + ions in the gas phase (MS) and in DMSO-d 6 solution (NMR) has been observed. The ''internal'' H-bonds (N1HÁ Á ÁO6) are stronger than the ''external'' ones (N7HÁ Á ÁO2) in these clusters (NMR). Fig. 1 Tetrads composed of 7H-3-methylxanthine (3MX) and different cations [cat + = none, Na + , K + , NH 4 + ; purine atom and spectroscopic (underlined) numbering shown in upper left ring].

Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry

“…A range of noncovalent clusters with different cations are observed in the gas phase, in agreement with Szolomájer et al [10]. When ammonium acetate is added as a solvent modifier, abundant peaks correspond to tetrameric species with alkali metal and ammonium cations ( Figure 1a); for example [(3-MX) 4 [10,12,13] by many singly (Figure 1a), doubly (Figure 1b-d), and multiply (Figure 1d) charged species, making it difficult to identify which species are present because of the overlapping isotopic patterns.…”

“…3-MX has been studied by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance by Szolomájer et al [10]; mass spectral data for a single tetrameric complex of 3-MX (or tetrad) and an octameric species composed of two parallel tetrads were reported. Here we report a study using ESI combined with a prototype FAIMS device and orthogonal acceleration time-of-flight (TOF) MS, to investigate noncovalently bound, supramolecular complexes of (3-MX) n .…”

“…3-Methylxanthine (3-MX) is an example of a small molecule that can form stable noncovalently bound supramolecular complexes in the gas phase [10]. 3-MX has been shown to selfassemble in the presence of alkali metals and ammonium ions to form clusters around a stabilizing cation, as shown in Structure1; the 3-MX purine base contains both hydrogen bond donor [NH (1) and O(2)) and acceptor (NH(7) and O(6)] groups [11][12][13].…”

Studies of ruthenium(ii)-2,2′-bisimidazole complexes on binding to G-quadruplex DNA and inducing apoptosis in HeLa cells

“…They found that the complex damaged the sequences by photobridging intramolecularly two or more G bases with the metallic [(tap) 2-Ru(tpac)Ru(tap) 2 ] 4+ . We designed three new complexes [Ru(bpy) 2 (biim)] 2+ (1), [Ru(phen) 2 (biim)] 2+ (2) and [Ru(p-mopip) 2 -(biim)] 2+ (3), all the three complexes have bisimidazole as the main ligand (Scheme 1). 22 Thomas et al reported that the dinuclear tppz-based systems could bind with high affinity to quadruplex DNA at high ionic strengths through the 22-mer d(AG 3 3 ] human telomeric sequence.…”

The expanding utility of continuous flow hydrogenation

“…[51][52][53][54][55] Generally conditions for Bn group removal entail use of 10% Pd/C catalyst at >40 bar and >40°C, [52][53][54][56][57][58] with Cbz groups are amenable to removal at lower temperatures and pressures. [51][52][53][54][55] Generally conditions for Bn group removal entail use of 10% Pd/C catalyst at >40 bar and >40°C, [52][53][54][56][57][58] with Cbz groups are amenable to removal at lower temperatures and pressures.…”