Copper (I) SNS Pincer Complexes: Impact of Ligand Design and Solvent Coordination on Conformer Interconversion from Spectroscopic and Computational Studies

The syntheses and detailed characterizations (X-ray crystallography, NMR spectroscopy, cyclic voltammetry, infrared spectroscopy, electrospray mass spectrometry, and elemental analyses) of two new Cu(I) pincer complexes are reported. The pincer ligand coordinates through one nitrogen and two sulfur donor atoms and is based on bis-imidazole or bis-triazole precursors. These tridentate SNS ligands incorporate pyridine and thione-substituted imidazole or triazole functionalities with connecting methylene units that provide flexibility to the ligand backbone and enable high bite-angle binding. Variable temperature 1H NMR analysis of these complexes and of a similar zinc(II) SNS system shows that all are fluxional in solution and permits the determination of ΔGexp‡ and ΔSexp‡. DFT calculations are used to model the fluxionality of these complexes and indicate that a coordinating solvent molecule can promote hemilability of the SNS ligand by lowering the energy barrier involved in the partial rotation of the methylene units

Opportunities for Patient-centered Outcomes Research in Radiology

Recently created in 2010, the Patient-Centered Outcomes Research Institute (PCORI) supports patient-centered comparative effectiveness research with a focus on prioritizing high-impact studies and improving trial design methodology. The Association of University Radiologists Radiology Research Alliance Task Force on patient-centered outcomes research in Radiology aims to review recently funded imaging-centric projects that adhere to the methodologies established by PCORI. We provide an overview of the successful application of PCORI standards to radiology topics, highlight how these methodologies differ from other forms of radiology research, and identify opportunities for new projects as well as potential barriers for involvement. Our hope is that review of specific case examples in radiology will clarify the use and value of PCORI methods mandated and supported nationally by the Affordable Care Act

Clinical Applications of 3D Printing: Primer for Radiologists

Three-dimensional (3D) printing refers to a number of manufacturing technologies that create physical models from digital information. Radiology is poised to advance the application of 3D printing in health care because our specialty has an established history of acquiring and managing the digital information needed to create such models. The 3D Printing Task Force of the Radiology Research Alliance presents a review of the clinical applications of this burgeoning technology, with a focus on the opportunities for radiology. Topics include uses for treatment planning, medical education, and procedural simulation, as well as patient education. Challenges for creating custom implantable devices including financial and regulatory processes for clinical application are reviewed. Precedent procedures that may translate to this new technology are discussed. The task force identifies research opportunities needed to document the value of 3D printing as it relates to patient care

Logistics of Three-dimensional Printing: Primer for Radiologists

The Association of University Radiologists Radiology Research Alliance Task Force on three-dimensional (3D) printing presents a review of the logistic considerations for establishing a clinical service using this new technology, specifically focused on implications for radiology. Specific topics include printer selection for 3D printing, software selection, creating a 3D model for printing, providing a 3D printing service, research directions, and opportunities for radiologists to be involved in 3D printing. A thorough understanding of the technology and its capabilities is necessary as the field of 3D printing continues to grow. Radiologists are in the unique position to guide this emerging technology and its use in the clinical arena

Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small-molecule magnetic resonance probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis non-invasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that, for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, makes them strong candidates for clinical translation

Tailored Chemical Reactivity Probes for Systemic Imaging of Aldehydes in Fibroproliferative Diseases

During fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small-molecule magnetic resonance probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis non-invasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that, for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, makes them strong candidates for clinical translation