Five novel generations of phosphorus dendrimers based on a cyclotriphosphazene core with stable TEMPO radicals end groups have been synthesized and studied by EPR, SQUID, 1 H NMR, 31 P NMR, FT-IR, and UV−vis spectroscopy. The nitroxyl radicals exhibit a strong exchange interaction, which depends on the dendrimer generation and the temperature. An |Δm s | = 2 transition has been observed in each generation in dilution conditions demonstrating the intramolecular origin of the radicals interaction. There exists a direct proportionality between the EPR |Δm s | = 2 transition intensity and the number of radicals by generation; consequently, the utility of EPR for the determination of the substitution efficiency on dendrimers by paramagnetic species is quite good. From the UV−vis characterization, we have observed that the molar extinction coefficient value is also proportional to the number of TEMPO groups. The magnetic properties of the zero, first and fourth generation dendrimers studied by SQUID magnetometry show antiferromagnetic interaction between radicals.

The finding of alternative imaging probes to Gadolinium (Gd) and other metal based contrast agents (CA) is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of an entirely organic metal-free magnetic resonance imaging (MRI) contrast agent based on polyphosphorhydrazone (PPH) dendrimers, fully functionalized with up to 48 organic nitroxide radical units. We propose an innovative synthetic procedure based on the use of an amino acid linker (Tyr) coupled to each dendrimer′s branch that permits the anchoring of the radicals and at the same time makes possible the control over their water solubility. We demonstrate that the negatively charged resulting PPH Gn-Tyr-PROXYL (n = 0–3) radical dendrimers are excellent candidates to be used as MRI contrast agents, suited for biomedical applications as they show high water solubility, no aggregation problems, and low cytotoxicity, as well as good stability in highly reducing environments. It is achieved a remarkable r 1 relaxivity, ca. four times higher (13 mM–1 s–1) than the gold-standard Gd-DTPA used in clinics. Furthermore, the r 1 and r 2 relaxivity per unit of radical showed an increase with the increase in generation of dendrimers.

Herein we report the synthesis and the study as polarizing agent for fast dissolution DNP of a novel mixed biradical with a BDPA and TEMPO radical units covalently bound by an ester group (BDPAesterTEMPO). Such a biradical exhibits an extremely high DNP NMR enhancement > 50000 which constitutes one of the largest signal enhancement observed so far, to the best of our knowledge. Dynamic nuclear polarization (DNP)1 is used for enhancement of nuclear magnetic resonance signals in both solid and liquid samples. , low concentration biological samples 5 or has been used for metabolic imaging applications. 6,7,8 The nature of the polarizing agent has a crucial role in the efficiency of DNP. In the case of dDNP, the effort has been focused in monoradicals, mainly trityl radicals like the well-known Ox63, 2 PTM 9 or BDPA 10 derivatives. The typical mechanism of choice to transfer electron magnetization is the "solid-effect" (SE), 11 and the ideal radical for such a mechanism will be a monoradical with a narrow EPR line like Ox63, however it has been shown to form oligomers that may limit its efficiency. 12 On the other hand, biradicals are of considerable interest as polarizing agents for MAS-DNP experiments. 13,14 The development of high-field MAS-DNP has mainly focused on the cross-effect (CE) mechanism 15,16,17 which is one of the mechanisms for which a large signal enhancement is expected for biradicals, since typical SE enhancements are considerably lower. 13 Up to now, the most successful biradicals so far, used for MAS-DNP in solid-state NMR applications, particularly to study biological solids, new materials and studies of material surfaces 3,4,18 are based on two radicals of the same type (nitroxides) combined in the proper orientation and distance. 14,19,20 It is known that the ideal CE polarizing agent would be a biradical with an EPR spectrum consisting of two sharp lines separated by the Larmor frequency of the nuclei to be polarized, ω 0S1 -ω 0S2 ≈ ω 0I . However, only a few known radicals exhibit spectral narrow lines, e. g. trityl radicals and BDPA radical derivatives, which have similar isotropic g-values. 21 As TEMPO derivatives have a broad line with significant spectral density at a frequency separation matching ω 0I , using a narrow line radical such as trityl or BDPA together with TEMPO could be a reasonable approximation. On the other hand, it is known that for an efficient cross effect mechanism, the dipolar coupling, in conjunction with the J-coupling, leads to the state mixing that is critical for it. 17 Some mixed nitroxide-trityl biradicals had been described as EPR sensors of the redox state of cells 22 or others 23 but had not been tested for DNP. The Griffin group has demonstrated the goodness of using some physical mixtures of two different radical species 13,24,25 and, recently, the use of a mixed biradical for MAS-DNP. 26Under dDNP, the efficiency of TEMPO-based biradicals is not optimal due to the difficulties to efficiently irradiate the full broad EPR lineshape at low temperature...