Substituted tetrazines have been found to undergo facile inverse electron demand Diels-Alder reactions with "tunable" reaction rates.

Hypoxia is a significant feature of solid tumor cancers. Hypoxia leads to a more malignant phenotype that is resistant to chemotherapy and radiation, is more invasive and has greater metastatic potential. Hypoxia activates the hypoxia inducible factor (HIF) pathway, which mediates the biological effects of hypoxia in tissues. The HIF complex acts as a transcription factor for many genes that increase tumor survival and proliferation. To date, many HIF pathway inhibitors indirectly affect HIF but there have been no clinically approved direct HIF inhibitors. This can be attributed to the complexity of the HIF pathway, as well as to the challenges of inhibiting protein–protein interactions.

Carbon monoxide belongs to the family of signaling molecules and has been shown to possess therapeutic effects. Similar to NO, safe delivery of CO is a key issue in developing CO-based therapeutics. Herein we report a "click and release" CO-prodrug approach, which allows the release of CO under physiological conditions without the need for light irradiation. The system releases CO in a triggered and controllable manner and possesses the potential of tunable release rates.

Cycloaddition reactions involving tetrazine have proven to be powerful bioorthogonal tools for various applications. Conceivably, sequential and selective labeling using tetrazine-based reactions can be achieved by tuning the reaction rate. By varying the substituents on tetrazine, cycloaddition rate variations of over 200 fold have been achieved with the same dienophile. Coupled with the availability of different dienophiles, such as norbornene, the reaction rate difference can be over 14,000 folds. These substituted tetrazines can be very useful for selective labeling under different conditions.

The transportation of hazardous materials is always accompanied by considerable risk that will impact public and environment security. As an efficient and reliable transportation organization, a multimodal service should participate in the transportation of hazardous materials. In this study, we focus on transporting hazardous materials through the multimodal service network and explore the hazardous materials multimodal routing problem from the operational level of network planning. To formulate this problem more practicably, minimizing the total generalized costs of transporting the hazardous materials and the social risk along the planned routes are set as the optimization objectives. Meanwhile, the following formulation characteristics will be comprehensively modelled: (1) specific customer demands; (2) multiple hazardous material flows; (3) capacitated schedule-based rail service and uncapacitated time-flexible road service; and (4) environmental risk constraint. A bi-objective mixed integer nonlinear programming model is first built to formulate the routing problem that combines the formulation characteristics above. Then linear reformations are developed to linearize and improve the initial model so that it can be effectively solved by exact solution algorithms on standard mathematical programming software. By utilizing the normalized weighted sum method, we can generate the Pareto solutions to the bi-objective optimization problem for a specific case. Finally, a large-scale empirical case study from the Beijing–Tianjin–Hebei Region in China is presented to demonstrate the feasibility of the proposed methods in dealing with the practical problem. Various scenarios are also discussed in the case study.