Exploring Inner-Sphere Water Interactions of Fe(II) and Co(II) Complexes of 12-Membered Macrocycles To Develop CEST MRI Probes.

Several paramagnetic Co(II) and Fe(II) macrocyclic complexes were prepared with the goal of introducing a bound water ligand to produce paramagnetically shifted water 1H resonances and for paramagnetic chemical exchange saturation transfer (paraCEST) applications. Three 12-membered macrocycles with amide pendent groups including 1,7-bis(carbamoylmethyl)-1,4,7,10-tetraazacyclodocane (DCMC), 4,7,10-tris(carbamoylmethyl)-,4,7,10-triaza-12-crown-ether (N3OA), and 4,10-bis(carbamoylmethyl)-4,10-diaza-12-crown-ether (NODA) were prepared and their Co(II) complexes were characterized in the solid state and in solution. The crystal structure of [Co(DCMC)]Br2 featured a six-coordinated Co(II) center with distorted octahedral geometry, while [Co(NODA)(OH2)]Cl2 and [Co(N3OA)](NO3)2 were seven-coordinated. The analogous Fe(II) complexes of NODA and NO3A were successfully prepared, but the complex of DCMC oxidized rapidly to the Fe(III) form. Similarly, [Fe(NODA)]2+ oxidized over several days, forming crystals of the Fe(III) complex isolated as the µ-O bridged dimer. Magnetic susceptibility values and paramagnetic NMR spectra of the Fe(II) complexes of NODA and N3OA, as well as Co(II) complexes of DCMC, NODA, and N3OA, were consistent with high spin complexes. CEST peaks ranging from 60 ppm to 70 ppm, attributed to NH groups of the amide pendents, were identified. Variable-temperature 17O NMR spectra of Co(II) and Fe(II) NODA complexes were consistent with rapid exchange of the water ligand with bulk water. Notably, the Co(II) and Fe(II) complexes presented here produced substantial paramagnetic shifts of bulk water 1H resonances, independent of having an inner-sphere water.

Imidazole-Appended Macrocyclic Complexes of Fe(II), Co(II), and Ni(II) as ParaCEST Agents.

The solution chemistry and solid state structures of the Co(II), Fe(II), and Ni(II) complexes of N,N'-bis(imidazole-2-ylmethyl)-4,10-diaza-15-crown-5 (HINO) are reported. The Co(II) and Ni(II) complexes of HINO are the first examples of paraCEST agents (paramagnetic chemical exchange saturation transfer) that feature exchangeable imidazole NH protons. The crystal structures of [Co(HINO)]CoCl4·H2O and [Fe(HINO)](CF3SO3)2 have the metal ions coordinated to four nitrogen and three oxygen donor atoms of the macrocyclic ligand in a distorted pentagonal bipyramidal geometry. In [Ni(HINO)](CF3SO3)2, the nickel ion is bound to only two of the three ether oxygens and three nitrogens to produce a complex with a distorted octahedral geometry. The 1H NMR spectra of the three paramagnetic complexes show resonances characteristic of effective C2 symmetry in solution. CEST peaks attributed to the imidazole NH proton of the pendent group are observed at 32 and 55 ppm away from bulk water for [Co(HINO)]2+ and [Ni(HINO)]2+, respectively, on a 11.7 or 9.4 T NMR spectrometer. For both complexes, an optimal CEST effect was observed at pH 7.2, and the rate constant for proton exchange under these conditions was 1.0 × 103 s-1. [Fe(HINO)]2+ did not produce a CEST peak due to oxidation of the complex in water at neutral pH. The CEST peak of [Co(HINO)]2+ or [Ni(HINO)]2+ is observed in the presence of human serum albumin (HSA). These complexes show enhanced kinetic inertness toward dissociation in acid or in the presence of HSA in comparison to analogous complexes with amide pendent groups.

Placement and promotion strategies to increase sales of healthier products in supermarkets in low-income, ethnically diverse neighborhoods: a randomized controlled trial.

BACKGROUND: The greater presence of supermarkets in low-income, high-minority neighborhoods has the potential to positively affect diet quality among those at greatest risk of obesity. In-store marketing strategies that draw attention to healthier products may be effective, sustainable, and scalable for improving diet quality and health. Few controlled studies of in-store marketing strategies to promote sales of healthier items in low-income, high-minority neighborhoods have been conducted. OBJECTIVE: The objective of this study was to evaluate the effects of in-store marketing strategies to promote the purchase of specific healthier items in 5 product categories: milk, ready-to-eat cereal, frozen meals, in-aisle beverages, and checkout cooler beverages. DESIGN: The design was a cluster-randomized controlled trial conducted from 2011 to 2012. Eight urban supermarkets in low-income, high-minority neighborhoods were the unit of randomization, intervention, and analysis. Stores were matched on the percentage of sales from government food-assistance programs and store size and randomly assigned to an intervention or control group. The 4 intervention stores received a 6-mo, in-store marketing intervention that promoted the sales of healthier products through placement, signage, and product availability strategies. The 4 control stores received no intervention and were assessment-only controls. The main outcome measure was weekly sales of the targeted products, which was assessed on the basis of the stores' sales data. RESULTS: Intervention stores showed significantly greater sales of skim and 1% milk, water (in aisle and at checkout), and 2 of 3 types of frozen meals compared with control store sales during the same time period. No differences were found between the stores in sales of cereal, whole or 2% milk, beverages, or diet beverages. CONCLUSIONS: These data indicate that straightforward placement strategies can significantly enhance the sales of healthier items in several food and beverage categories. Such strategies show promise for significant public health effects in communities with the greatest risk of obesity.

Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range.