Unexpectedly large water-proton relaxivity of TEMPO incorporated into micelle-oligonucleotides

Abstract

Three lipid-oligonucleotides (ODN) carrying TEMPO were prepared and formed a micelle with a diameter of ca. 10 nm. The double strand ODN, lipid-polyT in DS, incorporating TEMPO near the core of the micelle showed the largest water-proton relaxivity, r 1 , value of 2.4 (25 MHz, 0.59 T) and 6.8 mM 21 s 21 (42 MHz, 1.0 T) per TEMPO.DNA derivatives carrying stable aminoxyls through various types of linkers have previously been prepared, revealing not only the conformation of various DNA strands but also their dynamics. 1 Such DNA double strands carrying organic spins could be expected to function as metal-free and large-size MRI agents, 2 taking advantage of the unique properties of the DNA strand, which binds to many water molecules in major and minor grooves for structural stabilization. 3 Recently, we reported that the double strand incorporating 5-uridine-TEMPO, UST, had relatively large water-proton relaxivity, r 1 , which is an indicative value for the contrast. 4 To increase the molecular size and further improve of the r 1 value, in this study DNA-micelles 5 carrying TEMPO, 2,2,6,6tetramethylpiperidine-N-oxyl, were prepared. The 15-mer of thymidine (polyT) and TEMPO-uridine (TDU) directly attached to the TEMPO radical without a linker, were selected as the base sequence and a spin source, respectively. We report the rotational correlation time, t R , and the relaxivities, r 1 , for their single-strand and double-strand micelles with complimentary strand (polyA), in addition to T 1 -weighted images in vitro (Fig. 1).The TDU monomer, was prepared by Suzuki coupling reaction; 5-iodo-29-deoxyuridine reacted with 4-borate TEMPO in the presence of tetrakis(triphenylphosphine)palladium(0). After pro-

Effective magnetic moment in cyclodextrin–polynitroxides: potential supramolecular vectors for magnetic resonance imaging

“…The relaxivity associated to 4-OH-TEMPO is consistent with the value reported in literature (0.28 mM À1 s À1 , in phosphate buffer at 25 C). 19 A slight increment of the relaxivity is observed with regard to the compound CD3. Probably, this effect could be associated to the higher molecular weight of CD3 compared to 4-OH-TEMPO.…”

Assessment of the Relaxation-Enhancing Properties of a Nitroxide-Based Contrast Agent TEEPO-Glc with In Vivo Magnetic Resonance Imaging

“…However, nitroxides with bulky side groups have shown remarkable stability in conditions mimicking biological matrix [23,24]. e research of nitroxide-based contrast agents comprises both macromolecular [25][26][27][28][29][30][31] and small molecule [32][33][34][35][36] systems. It is often considered that the advantage of using polymers or nanomaterials as a backbone for nitroxides is the possibility to attach several radical centers to the contrast agent molecule.…”

“…It is often considered that the advantage of using polymers or nanomaterials as a backbone for nitroxides is the possibility to attach several radical centers to the contrast agent molecule. Also, large molecules often have long rotational correlation times indicating their tumbling rates, which increases the relaxivity of the contrast agent [25]. However, increasing the size of the contrast agent molecule also has unfavorable e ects on tissue penetration and delivery [2].…”

Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity

“…1 MRI is based on the nuclear magnetic resonance phenomenon (NMR). 5,6 The parameter relaxivity (r 1,2 , units mM −1 s −1 ), defined as the selec- tive enhancement of the relaxation rates, R 1,2 (R 1,2 = 1/T 1,2 ), normalized to 1 mM concentration of paramagnetic centres, measures CA efficacy. 2,3 MRI is inherently non-invasive, makes use of (benign) non-ionizing radiation (static and radiofrequency magnetic fields), is depth independent and displays superb spatial resolution.…”

“…that by promoting selective reduction of T 1 or T 2 of the water protons of tissues can generate dramatic contrast enhancements. 5,6 The parameter relaxivity (r 1,2 , units mM −1 s −1 ), defined as the selec- † Electronic supplementary information (ESI) available. See DOI: 10.1039/ c4dt03210a a Centro de Química, Campus de Gualtar, Universidade do Minho, 4710-057 Braga, Portugal.…”