Quantifying the Effect of Guest Binding on Host Environment.

The environment around a host-guest complex is defined by intermolecular interactions between the complex, solvent molecules, and counterions. These interactions govern both the solubility of these complexes and the rates of reactions occurring within the host molecules and can be critical to catalytic and separation applications of host-guest systems. However, these interactions are challenging to detect using standard analytical chemistry techniques. Here, we quantify the hydration and ion pairing of a FeII4L4 coordination cage with a set of guest molecules having widely varying physicochemical properties. The impact of guest properties on host ion pairing and hydration was determined through microwave microfluidic measurements paired with principal component analysis (PCA). This analysis showed that introducing guest molecules into solution displaced counterions that were bound to the cage, and that the solvent solubility of the guest has the greatest impact on the solvent and ion-pairing dynamics surrounding the host. Specifically, we found that when we performed PCA of the measured equivalent circuit parameters and the solubility and dipole moment, we observed a high (>90%) explained variance for the first two principal components for each circuit parameter. We also observed that cage-counterion pairing is well-described by a single ion-pairing type, with a one-step reaction model independent of the type of cargo, and that the ion-pairing association constant is reduced for cargo with higher water solubility. Quantifying hydration and cage-counterion interactions is a critical step to building the next generation of design criteria for host-guest chemistries.

Coordination Cages Selectively Transport Molecular Cargoes Across Liquid Membranes.

Chemical purifications are critical processes across many industries, requiring 10-15% of humanity's global energy budget. Coordination cages are able to catch and release guest molecules based upon their size and shape, providing a new technological basis for achieving chemical separation. Here, we show that aqueous solutions of FeII4L6 and CoII4L4 cages can be used as liquid membranes. Selective transport of complex hydrocarbons across these membranes enabled the separation of target compounds from mixtures under ambient conditions. The kinetics of cage-mediated cargo transport are governed by guest binding affinity. Using sequential transport across two consecutive membranes, target compounds were isolated from a mixture in a size-selective fashion. The selectivities of both cages thus enabled a two-stage separation process to isolate a single compound from a mixture of physicochemically similar molecules.

Engineering Permanent Porosity into Liquids.

The possibility of engineering well-defined pores into liquid materials is fascinating from both a conceptual and an applications point of view. Although the concept of porous liquids was proposed in 2007, these materials had remained hypothetical due to the technical challenges associated with their synthesis. Over the past five years, however, reports of the successful construction of porous liquids based on existing porous scaffolds, such as coordination cages, organic cages, metal-organic frameworks, porous carbons, zeolites, and porous polymers, have started to emerge. Here, the focus is on these early reports of porous liquids as prototypes in the field, classified according to the previously defined types of porous liquids. Particular attention will be paid to design strategies and structure-property relationships. Porous liquids have already exhibited promising applications in gas storage, transportation, and chemical separations. Thus, they show great potential for use in the chemical industry. The challenges of preparation, scale-up, volatility, thermal and chemical stability, and competition with porous solids will also be discussed.

Guest Encapsulation within Surface-Adsorbed Self-Assembled Cages.

Coordination cages encapsulate a wide variety of guests in the solution state. This ability renders them useful for applications such as catalysis and the sequestration of precious materials. A simple and general method for the immobilization of coordination cages on alumina is reported. Cage loadings are quantified via adsorption isotherms and guest displacement assays demonstrate that the adsorbed cages retain the ability to encapsulate and separate guest and non-guest molecules. Finally, a system of two cages, adsorbed on to different regions of alumina, stabilizes and separates a pair of Diels-Alder reagents. The addition of a single competitive guest results in the controlled release of the reagents, thus triggering their reaction. This method of coordination cage immobilization on solid phases is envisaged to be applicable to the extensive library of reported cages, enabling new applications based upon selective solid-phase molecular encapsulation.

Computerized Clinical Decision Support to Prevent Venous Thromboembolism Among Hospitalized Patients: Proximal Outcomes from a Multiyear Quality Improvement Project.

Despite venous thromboembolism (VTE) policy initiatives, gaps exist between guidelines and practice. In response, hospitals implement clinical decision support (CDS) systems to improve VTE prophylaxis. To assess the impact of a VTE CDS on reducing incidence of VTE, this study used a pretest/posttest, longitudinal, cohort design incorporating electronic health record (EHR) data from one urban tertiary and level 1 trauma center, and one suburban hospital. VTE CDS was embedded into the EHR system. The study included 45,046 admissions; 171,753 patient days; and 110 VTE events. The VTE rate declined from 0.954 per 1,000 patient days to 0.434 comparing baseline to full VTE CDS. Compared to baseline, patients benefitting from VTE CDS were 35% less likely to have a VTE. VTE CDS utilization achieved 78.4% patients assessed within 24 hr from admission, 64.0% patients identified at risk, and 47.7% patients at risk for VTE with an initiated VTE interdisciplinary plan of care. CDS systems with embedded algorithms, alerts, and notification capabilities enable physicians at the point of care to utilize guidelines and make impactful decisions to prevent VTE. This study demonstrates a phased-in implementation of VTE CDS as an effective approach toward VTE prevention. Implications for future research and quality improvement are discussed as well.

Recommendations to improve the usability of drug-drug interaction clinical decision support alerts.

OBJECTIVE: To establish preferred strategies for presenting drug-drug interaction (DDI) clinical decision support alerts. MATERIALS AND METHODS: A DDI Clinical Decision Support Conference Series included a workgroup consisting of 24 clinical, usability, and informatics experts representing academia, health information technology (IT) vendors, healthcare organizations, and the Office of the National Coordinator for Health IT. Workgroup members met via web-based meetings 12 times from January 2013 to February 2014, and two in-person meetings to reach consensus on recommendations to improve decision support for DDIs. We addressed three key questions: (1) what, how, where, and when do we display DDI decision support? (2) should presentation of DDI decision support vary by clinicians? and (3) how should effectiveness of DDI decision support be measured? RESULTS: Our recommendations include the consistent use of terminology, visual cues, minimal text, formatting, content, and reporting standards to facilitate usability. All clinicians involved in the medication use process should be able to view DDI alerts and actions by other clinicians. Override rates are common but may not be a good measure of effectiveness. DISCUSSION: Seven core elements should be included with DDI decision support. DDI information should be presented to all clinicians. Finally, in their current form, override rates have limited capability to evaluate alert effectiveness. CONCLUSION: DDI clinical decision support alerts need major improvements. We provide recommendations for healthcare organizations and IT vendors to improve the clinician interface of DDI alerts, with the aim of reducing alert fatigue and improving patient safety.