Eight-Coordinate, Stable Fe(II) Complex as a Dual 19F and CEST Contrast Agent for Ratiometric pH Imaging

Accurate mapping of small changes in pH is essential to the diagnosis of diseases such as cancer. The difficulty in mapping pH accurately in vivo resides in the need for the probe to have a ratiometric response so as to be able to independently determine the concentration of the probe in the body independently from its response to pH. The complex FeII-DOTAm-F12 behaves as an MRI contrast agent with dual 19F and CEST modality. The magnitude of its CEST response is dependent both on the concentration of the complex and on the pH, with a significant increase in saturation transfer between pH 6.9 and 7.4, a pH range that is relevant to cancer diagnosis. The signal-to-noise ratio of the 19F signal of the probe, on the other hand, depends only on the concentration of the contrast agent and is independent of pH. As a result, the complex can ratiometrically map pH and accurately distinguish between pH 6.9 and 7.4. Moreover, the iron(II) complex is stable in air at room temperature and adopts a rare 8-coordinate g..

Synthesis, Structure, and Reactivity of Zirconium and Hafnium Imido Metalloporphyrins

The zirconium and hafnium porphyrin imido complexes (TTP)MNAriPr [TTP = meso-tetra-p-tolylporphyrinato dianion, M = Zr (1), Hf (2), AriPr = 2,6-diisopropylphenyl] were synthesized from (TTP)MCl2 and 2 equiv of LiNHAriPr. The zirconium imido complex, (TTP)ZrNAriPr, was also obtained from the preformed imido complex Zr(NAriPr)Cl2(THF)2 and (TTP)Li2(THF)2. Treatment of (TTP)HfCl2 with excess LiNH(p-MeC6H4) resulted in the formation of a bis(amido) complex, (TTP)Hf(NH-p-MeC6H4)2 (3), instead of an imido complex. In the presence of excess aniline, 2 formed an equilibrium mixture of bis(amido) compounds, (TTP)Hf(NHPh)(NHAriPr) and (TTP)Hf(NHPh)2. The nucleophilic character of the imido moiety is exhibited by its reaction with tBuNCO, producing isolable N,O-bound ureato metallacycles. The kinetic product obtained with zirconium, (TTP)Zr(η2-NAriPrC(NtBu)O) (4a), isomerized to (TTP)Zr(η2-NtBuC(NAriPr)O) (4b) in solution. Upon being heated to 80 °C, 4a produced the carbodiimide AriPrNCNtBu and a transient Zr(IV) oxo complex. The analogous hafnium complex (TTP)Hf(η2-NAriPrC(NtBu)O) (5a) did not eject the carbodiimide upon heating to 110 °C but isomerized to (TTP)Hf(η2-NtBuC(NAriPr)O) (5b). To support the formulation of 4a and 5a as N,O bound, the complex (TTP)Hf(η2-NAriPrC(NAriPr)O) (6) was studied by variable-temperature NMR spectroscopy. The corresponding thio- and selenoureato metallacycles were not isolable in the reaction between 1 and 2 with tBuNCS and tBuNCSe. Concomitant formation of the metallacycle with decomposition to the carbodiimide, AriPrNCNtBu, reflects the lower C−Ch bond strength in the proposed N,Ch-bound metallacycles. Treatment of 2 with 1,3-diisopropylcarbodiimide resulted in the η2-guanidino complex (TTP)Hf(η2-NAriPrC(NiPr)NiPr) (7a), which isomerized to the less sterically crowded isomer (TTP)Hf(η2-NiPrC(NAriPr)NiPr) (7b). Complexes 1, 2, 4a, 4b, and7a were characterized by X-ray crystallography. The monomeric terminal imido compounds, 1and 2, are isomorphous:  M−Nimido distances of 1.863(2) Å (Zr) and 1.859(2) Å (Hf); M−Nimido−C angles of 172.5(2)° (Zr) and 173.4(2)° (Hf). The structures of the ureato complexes 4aand 4b and the guanidino complex 7a exhibit typical alkoxido and amido bond distances (Zr−N = 2.1096(13) Å (4a), 2.137(3) Å (4b); Zr−O = 2.0677(12) Å (4a), 2.066(3) Å (4b); Hf−N = 2.087(2) Å, 2.151(2) Å (7a))

Addition and Metathesis Reactions of Zirconium and Hafnium Imido Complexes

The zirconium and hafnium imido metalloporphyrin complexes (TTP)MNAriPr (TTP = meso-5,10,15,20-tetra-p-tolylporphyrinato dianion; M = Zr (1), Hf; AriPr = 2,6-diisopropylphenyl) were used to mediate addition reactions of carbonyl species and metathesis of nitroso compounds. The imido complexes react in a stepwise manner in the presence of 2 equiv of pinacolone to form the enediolate products (TTP)M[OC(tBu)CHC(tBu)(Me)O] (M = Zr (2), Hf (3)), with elimination of H2NAriPr. The bis(μ-oxo) complex [(TTP)ZrO]2 (4) is formed upon reaction of (TTP)ZrNAriPr with PhNO. Treatment of compound 4 with water or treatment of compound 2 with acetone produced the (μ-oxo)bis(μ-hydroxo)-bridged dimer [(TTP)Zr]2(μ-O)(μ-OH)2 (5). Compounds 2, 4, and 5 were structurally characterized by single-crystal X-ray diffraction

The Effect of Ordered Water on a Short, Strong (Speakman-Hadži) Hydrogen Bond

We have determined the structures of the sodium, tetrabutylam- monium (TBA) and bis(triphenylphosphoranylidene)ammonium (PNP) salts of the bis(4-nitrophenoxide) anion by X-ray crystallography. The sodium salt is a dihydrate, with the water oxygens coordinated to the sodium cations, and one hydogen from each water hydrogen bonded to one of the bridging oxygens of the anion. The TBA and PNP salts are anhydrous. Nevertheless the oxygen- oxygen distance is shortest in the sodium salt; 246.5 pm in the sodium salt, 247.5 pm in the TBA salt, and 249 pm in the PNP salt; suggesting that the hydrogen bond is not weakened by the water, and may be strongest in the hydrated salt. (All three compounds show Hadži type ii IR spectra, and are called Speakman-Hadži compounds in this paper.) The 2H chemical shifts of the bridging hydrogen in the three solids are 16.8 ppm for the sodium salt, 16.8 ppm for the TBA salt, and 16.5 ppm for the PNP salt. Again there is no evidence that the water weakens the hydrogen bond. These results can be understood by noting that the additional hydrogen bonds to the bridging oxygens decrease their proton affinity, but the mutual repulsion of the oxygens is also decreased