Search Results (4)

We investigated the effect of different organic coatings on the ¹H-NMR relaxation properties of ultra-small iron-oxide-based magnetic nanoparticles. The first set of nanoparticles, with a magnetic core diameter $d_{s_1}$ = 4.4 ± 0.7 nm, was coated with polyacrylic acid (PAA) and dimercaptosuccinic acid (DMSA), while the second set, $d_{s_2}$ = 8.9 ± 0.9 nm, was coated with aminopropylphosphonic acid (APPA) and DMSA. At fixed core diameters but different coatings, magnetization measurements revealed a similar behavior as a function of temperature and field. On the other hand, the ¹H-NMR longitudinal $r_1$ nuclear relaxivity in the frequency range $\nu$ = 10 kHz ÷ 300 MHz displayed, for the smallest particles (diameter $d_{s_1}$), an intensity and a frequency behavior dependent on the kind of coating, thus indicating different electronic spin dynamics. Conversely, no differences were found in the $r_1$ relaxivity of the biggest particles ($d_{s_2}$) when the coating was changed. It is concluded that, when the surface to volume ratio, i.e., the surface to bulk spins ratio, increases (smallest nanoparticles), the spin dynamics change significantly, possibly due to the contribution of surface spin dynamics/topology. Full article

Simple and efficient strategies for the syntheses of enantiomerically enriched functionalized diethyl 2-amino-, 2,3-diamino- and 2-amino-3-hydroxypropylphosphonates have been developed starting from, respectively, N-protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl (R)- and (S)-2-(N-Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of (R)- and (S)-N-Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected (R)- and (S)-2,3-diaminopropylphosphonates were synthesized from (R)- and (S)-N-Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of (R)- and (S)-2-(N-Boc-amino)-3-azidopropylphosphonates using triphenylphosphine. On the other hand, treatment of the corresponding (R)- and (S)-N-Bn-(aziridin-2-yl)methylphosphonates with glacial acetic acid led regiospecifically to the formation of (R)- and (S)-2-(N-Bn-amino)-3-acetoxypropylphosphonates. Full article

(1) Background: The acidosis of the tumor micro-environment may have profound impact on cancer progression and on the efficacy of treatments. In the present study, we evaluated the impact of a treatment with UK-5099, a mitochondrial pyruvate carrier (MPC) inhibitor on tumor extracellular pH (pHe); (2) Methods: glucose consumption, lactate secretion and extracellular acidification rate (ECAR) were measured in vitro after exposure of cervix cancer SiHa cells and breast cancer 4T1 cells to UK-5099 (10 µM). Mice bearing the 4T1 tumor model were treated daily during four days with UK-5099 (3 mg/kg). The pHe was evaluated in vivo using either chemical exchange saturation transfer (CEST)-MRI with iopamidol as pHe reporter probe or ³¹P-NMR spectroscopy with 3-aminopropylphosphonate (3-APP). MR protocols were applied before and after 4 days of treatment; (3) Results: glucose consumption, lactate release and ECAR were increased in both cell lines after UK-5099 exposure. CEST-MRI showed a significant decrease in tumor pHe of 0.22 units in UK-5099-treated mice while there was no change over time for mice treated with the vehicle. Parametric images showed a large heterogeneity in response with 16% of voxels shifting to pHe values under 7.0. In contrast, ³¹P-NMR spectroscopy was unable to detect any significant variation in pHe; (4) Conclusions: MPC inhibition led to a moderate acidification of the extracellular medium in vivo. CEST-MRI provided high resolution parametric images (0.44 µL/voxel) of pHe highlighting the heterogeneity of response within the tumor when exposed to UK-5099. Full article

All possible isomers of 1,2,3-tri(N-tert-butoxycarbonylamino)propylphosphonate 6 were synthesized from the respective diethyl [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates 5 via opening the aziridine ring with trimethylsilyl azide (TMSN₃) followed by hydrogenolysis in the presence of di-tert-butyl dicarbonate (Boc₂O). [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1R,2R,1′S)-5a and (1S,2S,1′R)-5c were smoothly transformed into diethyl 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates (1R,2R,1′S)-9a and (1S,2S,1′R)-9c, respectively by the opening of the aziridine ring with acetic acid. Transformations of [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1S,2R,1′S)-5b and (1R,2S,1′R)-5d into diethyl 3-acetoxy-1-benzylamino-2-[(1-phenylethyl)amino]propylphosphonates (1S,2R,1′S)-9b and (1R,2S,1′R)-9d were accompanied by the formation of ethyl {1-(N-benzylacetamido)-3-hydroxy-2-[(1-phenylethyl)amino]propyl}phosphonate (1S,2R,1′S)-10b and (1R,2S,1′R)-10d and 3-(N-benzylacetamido)-4-[N-(1-phenylethyl)]amino-1,2-oxaphospholane (3S,4R,1′S)-11b and (3R,4S,1′R)-11d as side products. Diethyl (1R,2R)-, (1S,2S)-, (1S,2R)- and (1R,2S)-3-acetoxy-1,2-di(N-tert-butoxycarbonylamino)propylphosphonates 7a–7d were obtained from the respective 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates 9a–9d by hydrogenolysis in the presence of Boc₂O. Full article