Head‐to‐Head Right‐Handed Cross‐Links of the Antitumor‐Active Bis(μ‐N,N′‐di‐p‐tolylformamidinato)dirhodium(II,II) Unit with the Dinucleotides d(GpA) and d(ApG)

Abstract

Reactions of cis-[Rh(2)(DTolF)(2)(NCCH(3))(6)](BF(4))(2) with the dinucleotides d(GpA) and d(ApG) proceed to form [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}], respectively, with bridging purine bases spanning the Rh-Rh unit in the equatorial positions. Both dirhodium adducts exhibit head-to-head (HH) arrangement of the bases, as indicated by the presence of H8/H8 NOE cross-peaks in the 2D ROESY NMR spectra. The guanine bases bind to the dirhodium core at positions N7 and O6, a conclusion that is supported by the absence of N7 protonation at low pH values and the notable increase in the acidity of the guanine N1H sites (pK(a) approximately 7.4 in 4:1 CD(3)CN/D(2)O), inferred from the pH-dependence titrations of the guanine H8 proton resonances. In both dirhodium adducts, the adenine bases coordinate to the metal atoms through N6 and N7, which induces stabilization of the rare imino tautomer of the bases with a concomitant substantial decrease in the basicity of the N1H adenine sites (pK(a) approximately 7.0-7.1 in 4:1 CD(3)CN/D(2)O), as compared to the imino form of free adenosine. The presence of the adenine bases in the rare imino form is further corroborated by the observation of DQF-COSY H2/N1H and ROE N1H/N6H cross-peaks in the 2D NMR spectra of [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}] in CD(3)CN at -38 degrees C. The 2D NMR spectroscopic data and the molecular modeling results suggest the presence of right-handed variants, HH1R, in solution for both adducts (HH1R refers to the relative base canting and the direction of propagation of the phosphodiester backbone with respect to the 5' base). Complete characterization of [Rh(2)(DTolF)(2){d(GpA)}] and [Rh(2)(DTolF)(2){d(ApG)}] by 2D NMR spectroscopy and molecular modeling supports anti-orientation of the sugar residues for both adducts about the glycosyl bonds as well as N- and S-type conformations for the 5'- and 3'-deoxyribose residues, respectively.

NMR Spectroscopic Study of Tautomerism in Solution and in the Solid State

“…detected [108]. Presence of the still missing C(6)=NH imino form in nucleotides was confirmed by double quantum filtered-correlation spectroscopy (DQF-COSY) NMR experiments at low temperature [109]. For the first time, the N-H(7)/N-H(9) tautomeric equilibrium of a series of 6-substituted purine derivatives 64 (Scheme 5.47) could be frozen at 213 K in DMF-d 7 and quantified [106].…”

“…For the first time, the N-H(7)/N-H(9) tautomeric equilibrium of a series of 6-substituted purine derivatives 64 (Scheme 5.47) could be frozen at 213 K in DMF-d 7 and quantified [106]. The assignment of the tautomers is based on the characteristic 13 [109]. Also, 2 J C,H and 3 J C,H (distinguished by the sign of the couplings) between N(7)-H and C-5/C-4 were employed to assign the major of two solution-state tautomers of a 2,6-diaminopurine derivative to be the N(7)-H besides the N(9)-H form [110].…”

Photoinduced interactions of two dirhodium complexes with d(GTCGAC)2 probed by 2D NOESY

“…8 Dirhodium complexes have been previously shown to bind covalently to DNA in a manner similar to cisplatin and to exhibit antitumor activity. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Photodynamic therapy (PDT) is a technique currently in use that circumvents the systemic toxicity associated with traditional chemotherapy drugs. The drugs used for PDT are only cytotoxic upon light activation, thus providing spatiotemporal control of the activity.…”

Insights Into Metal−π Arene Interactions of the Highly Lewis Acidic Rh24+ Core with a Broad Set of π-Ligands: From Ethylene to Corannulene and C60-Fullerene

“…Over the years, we have revealed a remarkable reactivity of highly electrophilic dirhodium(II) tetratrifluoroacetate in inorganic, organometallic and supramolecular reactions . Moreover, the applications of the dirhodium core compounds span such diverse areas as catalysis, antitumor metallopharmaceuticals, phototheraupeutic agents, photochemistry, and self-assembly processes . However, no systematic theoretical insight into rhodium(II) binding affinities has been given.…”