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Cancer is among the leading causes of death worldwide. Although a number of new treatment options have been developed in recent years, there remains a need for improved chemotherapies. The primary challenges facing new cancer drugs include: (1) improving patient quality of life, (2) overcoming drug resistance and (3) lowering reoccurrence rates. Major drawbacks of current chemotherapeutics arise from poor selectivity towards cancer cells, dose limiting toxicities, compliance-reducing side effects, and an inability to address resistance mechanisms. Chemotherapeutics that fail to achieve complete eradication of the disease can also lead to relapse and promote treatment resistance. New strategies to overcome these drawbacks include the use of transition metal chelators and ionophores to alter selectively the concentrations of iron, copper, and zinc in cancer cells. A number of metal chelators have successfully demonstrated cytotoxicity and targeted activity against drug-resistant cancer cells; several have proved effective against cancer stem cells, a significant cause of tumour reoccurrence. However, problems with formulation and targeting have been noted. Recent efforts have thus focused on the design of pro-chelators, inactive versions of chelators that are designed to be activated in the tumour. This is an appealing strategy that may potentially increase efficacy towards cancer-resistant malignant cells. This Tutorial Review summarizes recent progress involving transition metal chelators, pro-chelators, and ionophores as potential cancer chemotherapeutics. We will focus on the reported agents that are able to coordinate iron, copper, and zinc.

[2.2]Paracyclophane (PCP) is a prevalent scaffold that is widely utilized in asymmetric synthesis, π-stacked polymers, energy materials, and functional parylene coatings that finds broad applications in bio- and materials science. In the last few years, [2.2]paracyclophane chemistry has progressed tremendously, enabling the fine-tuning of its structural and functional properties. This Minireview highlights the most important recent synthetic developments in the selective functionalization of PCP that govern distinct features of planar chirality as well as chiroptical and optoelectronic properties. Special focus is given to the function-inspired design of [2.2]paracyclophane-based π-stacked conjugated materials by transition-metal-catalyzed cross-coupling reactions. Current synthetic challenges, limitations, as well as future research directions and new avenues for advancing cyclophane chemistry are also summarized., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We report the synthesis and catalytic application of a highly stable distance-defined Au/Ru heterobimetallic complex. [2.2]Paracyclophane serves as a backbone, holding the two metal centers in a spatial orientation and metal-metal fixed distance. The Au/Ru heterobimetallic complex is highly stable, easily accessible and exhibits promising catalytic activity in a visible-light mediated dual Au/Ru Meyer-Schuster rearrangement.

New catalysts for important C-N bond formation are highly sought after. In this work, we demonstrate the synthesis and viability of a new class of planar chiral [2.2]paracyclophane-based bisoxazoline (BOX) ligands for the copper-catalyzed N-H insertion of α-diazocarbonyls into anilines. The reaction features a wide substrate scope and moderate to excellent yields, and delivers the valuable products at ambient conditions.

In this perspective, we review those stereoselective photocatalytic reactions that use synergy between photoredox catalysts and transition metal catalysts. In particular, we highlight the orchestrated interaction between two and more metals which not only enhance the turnover numbers, but also lead to increased selectivities. Aspects of green chemistry and sustainable developments are included. In this review, C-C, C-O, C-N and C-S forming reactions are discussed and a perspective on future developments is given.

This work presents a new approach to prepare mono- and disubstituted linear rigid bimetallic [2.2]paracyclophane-porphyrin conjugates via palladium-mediated Stille cross-coupling reaction. The metalated porphyrin moiety can be varied allowing convenient access to modular metal-metal fixed-distance Cu/Zn complexes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

We report a new Suzuki cross-coupling protocol for high yielding derivatization of [2.2]paracyclophane with pyridyl and pyrimidyl substituents. The [2.2]paracyclophane trifluoroborate salt presented herein is a bench stable, easily accessible, and convenient substitute to former cross-coupling substrates. This will be of very high interest for future paracyclophane derivatization endeavors., Competing Interests: The authors declare no competing financial interest.

Planar chiral [2.2]paracyclophane-based ligands and employment of such enantiopure representative ligands to facilitate selective transformation of prochiral or racemic substances into enantiopure products are rarely explored compared to the complex chiral scaffolds such as ferrocenes. This tutorial discusses recent findings and inspiring progress in design, synthetic tunability and applications of planar chiral [2.2]paracyclophane systems as a practical class of catalysts for asymmetric synthesis. Here, we summarize a series of planar chiral [2.2]paracyclophanes that are becoming an important new tool-box in asymmetric synthesis, employed in a variety of synthetic venues such as new chiral ligands and catalysts for stereo-controlled and enantioselective addition of alkyl, alkenyl, alkynyl and aryl zinc reagents to aliphatic and aromatic aldehydes, ketones, imines and many more. Besides, planar chiral [2.2]paracyclophanes are useful synthons, from a material perspective, can be incorporated into conjugated polymeric systems for chiroptical and optoelectronic properties, find broad applications in bio- and materials science, for instance, gold-based cytostatics, surface-mounted chiral MOF thin films for selective adsorption or in functionalized parylene polymer coatings, to name a few. This is an up-to-date tutorial review, written exclusively on planar chiral [2.2]paracyclophane chemistry, covering key aspects of synthesis, structures, properties, applications and future directions of chiral polymeric assemblies and novel biomaterials built with [2.2]paracyclophanes.

Objective: To develop a sensitive and specific nutrition screening tool that conforms to the requirements of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and is effective in any given hospital population., Design: A two-step prospective evaluation was performed in two unrelated community hospitals to determine the effectiveness of a current nutrition screening tool, and to develop a new, more sensitive tool that permits efficient use of available personnel., Statistical Analyses: Standard calculations for sensitivity, specificity, positive predictive value, and negative predictive value were used to compare the results of various screening methods with those of full nutrition assessments. Stepwise discriminant analysis was used to determine specific parameters that contributed to the diagnosis of malnutrition and to derive a predictive equation based on these parameters., Methods: In part 1, 100 patients admitted consecutively were evaluated using a subjective screening tool; the results were compared with those from full nutrition assessment of the same patients. Stepwise discriminant analysis identified three parameters most closely related to malnutrition, and a multivariant equation relative to nutrition risk was derived. In part 2, 151 randomly selected adult medical and surgical patients were evaluated at admission with the same screening tool used in part 1. Additionally, prealbumin level was determined on admission. The results of the screening, the discriminant analysis equation from part 1, and both methods incorporating the prealbumin level were compared with the results of a full nutrition assessment., Results: In part 1, discriminant analysis identified total lymphocyte count, percentage weight loss, and serum albumin level as the three best indicators of malnutrition. A multivariant equation incorporating these objective parameters was derived. In part 2, the equation yielded better sensitivity and specificity results than other screening methods. Inclusion of prealbumin level did not improve screening methods., Conclusions: The revised screening tool described can be used as the basis of an effective screening program that meets the proposed JCAHO nutrition care standards.

Background: The study was designed to quantitate factors such as preparation time, waste, and contamination associated with three different feeding systems for peptide-based diets and to determine appropriate hang times., Methods: Intensive care unit patients were randomized to receive a peptide-based diet in 1500-mL prefilled, sterile closed-system containers (CS) infused more than 24 hours, as open systems decanted from cans (OS-Can), or as open systems mixed from powder (OS-Powder). Open-system groups were provided a 12-hour supply twice daily in commercially clean 1-L bags with preattached sets. Samples were taken for culture during preparation and after infusion. Preparation time, initial and final microbial concentrations, and total waste were quantified., Results: Preparation time was significantly shorter for CS than for OS-Can or for OS-Powder (2 minutes vs 7.5 minutes vs 13.0 minutes). Initially, 100% of the OS-Powder and 30% of the OS-Can bags were contaminated, with significant contamination exceeding 10(4) colony-forming units/mL in 40% and in 5% of the bags, respectively. On final culture, significant contamination occurred in only 2% of the CS bags compared with 83% of the OS-Powder and 60% of the OS-Can bags. Average time from potential initial contamination to final culture in CS was 49.9 hours vs 38.8 hours for OS-Can and 32 hours for OS-Powder. Total waste was greater in CS than in OS-Can or OS-Powder but could be eliminated by extending allowable hang times., Conclusions: Nonvented closed-delivery containers may be safely infused for up to 48 hours. They are associated with reduced labor and contamination.