ABSTRACT
The ligand L(bip), containing two bidentate pyrazolyl-pyridine termini separated by a 3,3'-biphenyl spacer, has been used to prepare tetrahedral cage complexes of the form [M(4)(L(bip))(6)]X(8), in which a bridging ligand spans each of the six edges of the M(4) tetrahedron. Several new examples have been structurally characterized with a variety of metal cation and different anions in order to examine interactions between the cationic cage and various anions. Small anions such as BF(4)(-) and NO(3)(-) can occupy the central cavity where they are anchored by an array of CH···F or CH···O hydrogen-bonding interactions with the interior surface of the cage, but larger anions such as naphthyl-1-sulfonate or tetraphenylborate lie outside the cavity and interact with the external surface of the cage via CH···π interactions or CH···O hydrogen bonds. The cages with M = Co and M = Cd have been examined in detail by NMR spectroscopy. For [Co(4)(L(bip))(6)](BF(4))(8) the (1)H NMR spectrum is paramagnetically shifted over the range -85 to +110 ppm, but the spectrum has been completely assigned by correlation of measured T(1) relaxation times of each peak with Co···H distances. (19)F DOSY measurements on the anions show that at low temperature a [BF(4)](-) anion diffuses at a similar rate to the cage superstructure surrounding it, indicating that it is trapped inside the central cage cavity. Furthermore, the equilibrium step-by-step self-assembly of the cage superstructure has been elucidated by detailed modeling of spectroscopic titrations at multiple temperatures of an acetonitrile solution of L(bip) into an acetonitrile solution of Co(BF(4))(2). Six species have been identified: [Co(2)L(bip)](4+), [Co(2)(L(bip))(2)](4+), [Co(4)(L(bip))(6)](8+), [Co(4)(L(bip))(8)](8+), [Co(2)(L(bip))(5)](4+), and [Co(L(bip))(3)](2+). Overall the assembly of the cage is entropy, and not enthalpy, driven. Once assembled, the cages show remarkable kinetic inertness due to their mechanically entangled nature: scrambling of metal cations between the sites of pure Co(4) and Cd(4) cages to give a statistical mixture of Co(4), Co(3)Cd, Co(2)Cd(2), CoCd(3) and Cd(4) cages takes months in solution at room temperature.
ABSTRACT
The incorporation of C5-amino-modified 2'-deoxyuridine analogues into DNA have found application in nucleic acid labelling, the stabilization of nucleic acid structures, functionalization of nucleic acid aptamers and catalysts, and the investigation of sequence-specific DNA bending. In this study, we describe the physicochemical properties of four different C5-amino-modified 2'-deoxyuridines in which the amino group is tethered to the base via a 3-carbon alkyl, Z- or E-alkenyl or alkynyl linker. Conformational parameters of the nucleosides and their pK(a) values were deduced using 1H NMR. All of them display the expected anti-conformation of the nucleoside with 2'-endo sugar puckers for the deoxyribose ring. A preference for the cisoid conformation for the Z-alkenyl analogue is found, while the E-alkenyl analogue exists exclusively as its transoid conformation. The pK(a) values range from 10.0 for the analogue with an aliphatic propyl linker to 8.5 for the propargylamino analogue. The analogues have been used for the synthesis of triple-helix forming oligonucleotides (TFOs) in which they replace thymidine in the natural sequence. Oligonucleotides containing the propargylamino analogue display the highest stability especially at low pH, while those containing analogues with propyl and especially Z-alkenyl linkers are destabilized to a great extent. TFOs containing the analogue with the E-alkenyl linker have stability similar to the unmodified structures. The chemical synthesis of TFOs containing the analogue, 5-(3-hydroxyprop-1-ynyl)-2'-deoxyuridine that possesses a neutral but polar side chain show a remarkable stability, which is higher than that of all TFOs containing the alkylamino or alkenylamino analogues and only slightly lower than that of TFOs containing the propargylamino analogue. Both the hydroxyl and propargylamino substitutions impart enhanced triple-helix stability relative to the analogous sequences containing C5-propynyl-2'-deoxyuridine. Furthermore, a similar dependence of stability on pH is found between TFOs containing the hydroxypropynyl modifications and those containing the propargylamino side chains. This suggests that the major factor responsible for stabilizing such triple helices is due to the presence of the alkyne with an attached electronegative group.
