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The incorporation of multiple Fe(III) centers bridged by rigid ligands into a coordination cage represents a powerful approach for designing effective MRI contrast agents. In this context, an octahedral coordination cage with six high-spin Fe(III) centers is shown to be water soluble, robust towards dissociation and has effective relaxivity as a T1 MRI probe in solution and in mice. [ABSTRACT FROM AUTHOR]

Macrocyclic Co(II) complexes with appended amide‐glycinate groups were prepared to develop paramagnetic Co(II) chemical exchange saturation transfer (CEST) agents of reduced overall charge. Complexes with reduced charge and lowered osmolarity are important for their loading into liposomes and to provide complexes that are highly water soluble and well tolerated in animals. Co(L1) has two non‐coordinating benzyl groups and two amide‐glycinate pendants, whereas Co(L2) has two unsubstituted amide pendants and two amide‐glycinate pendants on cyclam (1,4,8,11‐tetraazacyclododecane). The 1H NMR spectrum of Co(L1) is consistent with a single cis‐pendant isomer with both amide protons in the trans‐configuration, as supported by an X‐ray crystal structure. Co(L2) has a mixture of different isomers in solution, including the trans‐1,4 and 1,8 pendant isomers. The Z‐spectrum of Co(L1) shows one highly‐shifted CEST peak, whereas Co(L2) exhibits six CEST peaks. Encapsulation of 40 mM Co(L1) in a liposome with osmotically‐induced shrinking at 300 mOsm/L produces a liposomal CEST agent with saturation frequency offset of 3 ppm. Addition of the amphiphilic 1,4,7‐triazacyclononane‐based complex Co(L5) to the liposomal bilayer at 18 mM with Co(L1) encapsulated in the liposome at 50 mM changes the sign and increases the magnitude of the saturation frequency offset to −7.5 ppm at 300 mOsm/L. [ABSTRACT FROM AUTHOR]

High-spin Fe(III) complexes of 1,4,7-triazacyclononane (TACN) with mixed oxygen donor pendants including hydroxypropyl, phenolate or amide groups are prepared for study as T1 MRI probes. Complexes with two hydroxypropyl pendants and either amide (Fe(TOAB)) or phenolate (Fe(PTOB)) groups are compared to an analog with three hydroxypropyl groups (Fe(NOHP)), in order to study the effect of the third pendant on the coordination sphere as probed by solution chemistry, relaxivity and structural studies. Solution studies show that Fe(PTOB) has two ionizations with the phenol pendant deprotonating with a pKa of 1.7 and a hydroxypropyl pendent with pKa of 6.3. The X-ray crystal structure of [Fe(PTOB)]Br2 features a six-coordinate complex with two bound hydroxypropyl groups, and a phenolate in a distorted octahedral geometry. The Fe(TOAB) complex has a single deprotonation, assigned to a hydroxypropyl group with a pKa value of 7.0. Both complexes are stabilized as high-spin Fe(III) in solution as shown by their effective magnetic moments and Fe(III)/Fe(II) redox potentials of −390 mV and −780 mV versus NHE at pH 7 and 25 °C for Fe(TOAB) and Fe(PTOB) respectively. Both Fe(PTOB) and Fe(TOAB) are kinetically inert to dissociation under a variety of challenges including phosphate/carbonate buffer, one equivalent of ZnCl2, two equivalents of transferrin or 100 mM HCl, or at basic pH values over 24 h at 37 °C. The r1 relaxivity of Fe(TOAB) at 1.4 T, pH 7.4 and 33 °C is relatively low at 0.6 mM−1 s−1 whereas the r1 relaxivity of Fe(PTOB) is more substantial and shows an increase of 2.5 fold to 2.5 mM−1 s−1 at acidic pH. The increase in relaxivity at acidic pH is attributed to protonation of the phenolate group to provide an additional pathway for proton relaxation. [ABSTRACT FROM AUTHOR]

Laboratory experiments that demonstrate the effect of paramagnetic complexes on chemical shifts and relaxation times of protons are a useful way to introduce magnetic resonance spectroscopy (MRS) probes or magnetic resonance imaging (MRI) contrast agents. In this undergraduate inorganic chemistry experiment, a paramagnetic Co(II) cage complex is prepared by reduction of a classical Co(III) cage complex. The Co(II) cage behaves as a paramagnetic shift agent (paraSHIFT) and produces relatively sharp and highly dispersed proton resonances. Comparison of the proton NMR spectra of the diamagnetic and paramagnetic cage complexes provides opportunities for students to consider coordination complex symmetry and the effect of unpaired electrons on the chemical shifts of proton resonances. Oxidation and spin state changes of transition metal complexes, Co(III)/Co(II), are also illustrated in this experiment.

Various studies are conducted to examine the cleavage of the diribonucleoside and the RNA analogues, which is mediated by an active dinuclear Zn(ll) catalyst, Zn(sub 2)(H (sub 2)O) giving it a transition-state stabilization. The results show that the transition state for the reaction between the zinc complex and the dinucleoside is stabilized by the interactions between the catalyst and the oxyanion of the basic alkoxy group.

A study is conducted on the recognition of uridine by the series of Zn(II) macrocyclic complexes and the design for the design of RNA cleavage catalysts. It is suggested that it may be possible to exploits Zn(II) macro cyclic complex interaction with uridine groups to increase the interaction of a tethered metal ion catalyst with RNA and to orient the catalyst with respect to the phosphate diester.

A dinuclear metal ion complex Zn2(L2O) and its mononuclear analogue Zn(L1OH) are synthesized and studied as catalysts of the cleavage of the phosphate diester 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP).

Research has been conducted on two bis(triazacyclononane) ligands that form the stable dinuclear Cu(II) complexes. The equilibrium modeling of pH-potentiometric measurements is discussed.