Open- and Closed-Loop Recycling: Highly Active Zinc Bisguanidine Polymerization Catalyst for the Depolymerization of Polyesters.

In this study, the aliphatic N,N-bisguanidine zinc complex [Zn(DMEG2ch)2](OTf)2·THF is introduced as a promising candidate for the chemical recycling of (bio)polyesters. This catalyst is highly active in the ring-opening polymerization (ROP) of lactide (LA) and ε­caprolactone (CL). The combination of polymerization and depolymerization activity creates new pathways towards a sustainable circular economy. The catalytic activity of [Zn(DMEG2ch)2](OTf)2·THF for the chemical recycling of polylactide (PLA) via alcoholysis was investigated by detailed kinetic and thermodynamic studies. It is shown that various high value-added alkyl lactates can be obtained efficiently under mild reaction conditions. Catalyst recycling was successfully tested using ethanol for the degradation of PLA. In addition, LA can be recovered directly from PLA, enabling either open- or closed-loop recycling. Selective PLA degradation from mixtures with polyethylene terephthalate (PET) and polymer blends are presented. For the first time, a cascade recycling reaction of a PLA/polycaprolactone (PCL) blend is tested with a zinc-based bisguanidine catalyst, whereby PLA is degraded selectively at first and subsequent modification of the reaction conditions leads to efficient degradation of the remaining PCL. The highly active, universally applicable benign zinc catalyst allows the implementation of a circular plastics economy and thus the reduction of plastic pollution in the environment.

Opportunities and Challenges of Establishing a Regional Bio-based Polylactic Acid Supply Chain.

Polylactic acid (PLA) is the bioplastic with the highest market share. However, it is mainly produced from first-generation feedstock and there are various inconsistencies in the literature in terms of its production and recycling processes, carbon footprint, and prices. The aim of this study is to compile and contrast these aspects and investigate second-generation PLA production from technical, economic, and ecological perspectives simultaneously. The comprehensive analyses also show the chances and challenges of originating a PLA supply chain in a specific region. Herein, the German Federal State of North Rhine-Westphalia (NRW) has been chosen as a region of interest. In addition to highlighting the industrial capabilities and synergies, the study quantifies and illustrates the locations of different suitable second-generation feedstocks in the region. However, the identified potentials can be challenged by various obstacles such as the high demand of bioresources, feedstock quality, spatial aspects, and logistics. Furthermore, the substantial price gap between PLA and fossil-based plastics can also discourage the investors to include PLA on their portfolios. Thus, the study also provides recommendations to overcome these obstacles and promote the regional value chains of bioplastics which may serve as prototype for other regions.

Rectal use of levetiracetam: best practice report for a stepwise approach for sustainable off-label decision making and treatment.

Off-label drug use is common practice in palliative care. It may pose a risk to the patient and benefit should outweigh harm. A decision and documentation aid for off-label use was developed to support practitioners in clinical practice off-label use. Using the example of the rectal administration of levetiracetam in three patient cases, the utilisation and benefits of the decision and documentation aid are presented and discussed. The rectal administration of levetiracetam clearly is an experimental treatment approach with little underlying evidence. To support and document the decision-making process for or against such an off-label use in clinical practice, it is helpful to have a structured approach in order to make this data comprehensible for a later point in time. Off-label use may be a permissible treatment alternative without underlying evidence, provided it takes place in a well-planned and well-monitored therapeutic setting and the benefits outweigh the potential risks.

Effective Ligand Design: Zinc Complexes with Guanidine Hydroquinoline Ligands for Fast Lactide Polymerization and Chemical Recycling.

Invited for this month's cover is the group of Sonja Herres-Pawlis at RWTH Aachen University. The image shows how the zinc guanidine complexes help a circular economy of bioplastics by mediating the ring-opening polymerization of lactide and the depolymerization of polylactide (PLA). The Research Article itself is available at 10.1002/cssc.202201075.

Effective Ligand Design: Zinc Complexes with Guanidine Hydroquinoline Ligands for Fast Lactide Polymerization and Chemical Recycling.

In this study, the synthesis of two new guanidine hydroquinoline ligands served as basis for six new zinc guanidine complexes. Two of these complexes showed very high activity in the lactide polymerization under industrial conditions. The lactide polymerization was demonstrated in solution and melt conditions observing high activity and molar masses up to 90 000 g mol-1 . Density functional theory studies elucidated the high activity of the complexes associated with the influence of the ligand backbone and the use of triflate counterions. On the way towards a circular economy, polymerization and depolymerization go hand in hand. So far, guanidine complexes have only shown their good activity in the ring opening polymerization of esters, and guanidine complexes with pure N donors have not been tested in recycling processes. Herein, the excellent ability of zinc guanidine complexes to catalyze both polymerization and depolymerization was demonstrated. The two most promising zinc complexes efficiently mediated the methanolysis of polylactide into methyl lactate under mild reaction conditions.

The Green toxicology approach: Insight towards the eco-toxicologically safe development of benign catalysts.

Green toxicology is a novel approach increasingly applied for the development of materials and chemicals that are more benign to the environment and human health than their conventional counterparts. It includes predictive eco-toxicological assessments of chemicals during the early developmental process to exclude adverse effects. In the present study, two guanidine zinc catalysts for the ring-opening polymerization of lactide were investigated using eco-toxicological tools. Namely, the fish embryo toxicity assay for teratogenic effects, the ER (α) CALUX assay for endocrine activity and the Ames fluctuation assay for mutagenic potential were applied. Both complexes showed no endocrine activity, mutagenicity or acute aquatic toxicity, however a delayed hatch could be observed, therefore suggesting potential effects on a molecular level. This proof-of-concept study aims to assess the toxicity of guanidine zinc catalysts and is a first step towards the incorporation of toxicological assessments into chemical developmental processes to achieve a sustainable and safe production of catalysts.

Drug Information Needs of Health Care Professionals in Palliative Care: A Retrospective Evaluation of a Palliative Care Drug Information Service.

CONTEXT: Drug therapy is an integral part of palliative care but pharmacotherapy can be challenging for health care professionals. Access to information is essential for health care providers to choose the best drug treatment for an individual patient. A drug information service can support health care professionals to obtain appropriate, unbiased information. OBJECTIVES: To describe the enquiries to a palliative care drug information service. Objectives are to determine the information needs (including off-label use) of different professional groups and areas of care, to identify subject areas and drug substances for which there is a high need for information. METHODS: Retrospective evaluation of all enquiries to a palliative care drug information service within 24 months from July 2017 to June 2019. RESULTS: During the study period, 477 enquiries reached the drug information service, mostly from physicians (59%), followed by pharmacists (31%). Ketamin was the most discussed drug (11%), in general enquiries or corresponding replies mostly contained drugs targeting the nervous system, such as analgesics. Application techniques (26%) was the most relevant category, cancer pain (24%) was the most frequently addressed symptom. About half of the enquiries (48%) dealt with off-label us, regarding an application mode outside the license. CONCLUSION: The information needs on palliative care pharmacotherapy seem to be particularly high among physicians. The demand for information in the area of application technology is particularly apparent and demonstrates a therapeutic gap in terms of availability of suitable preparations as well as necessary information.

Sedatives and Sedation at the End of Life in Nursing Homes: A Retrospective Multicenter Cohort Study.

OBJECTIVES: There is scarce information about sedation in nursing homes at the end of life. We aimed to assess (1) the use of sedatives generally and "sedatives with continuous effect," based on objective operational criteria, within the last week of life in nursing homes and (2) factors associated with this treatment. DESIGN: Retrospective cohort study, using the nursing homes' medical records. SETTING AND PARTICIPANTS: Residents who died in 4 German nursing homes from January 2015 to December 2017 and whose medical records were available (n = 512). METHODS: Sedatives analyzed were those recommended by guidelines for "palliative sedation": benzodiazepines, levomepromazine, haloperidol (≥5 mg/d), and propofol. The definition of "sedatives with continuous effect" and doses judged as at least moderately sedating were consented by palliative care clinicians and pharmacists, based on the literature. Descriptive statistics and multivariate logistic regression analysis were performed (R version 3.6.1). RESULTS: Overall, 110/512 (21%) deceased residents received a sedative at least once during the last week of life, 46/512 (9%) "sedatives with continuous effect." Oral lorazepam was used most frequently. Eleven of 512 (2%) residents received doses judged as at least moderately sedating. The term sedation was not used. Most frequent indications were agitation (58/110; 53%) and anxiety (35/110; 32%); no indication was noted for 36/110 (33%) residents. The resident's involvement in the decision for sedatives was documented in 3/110 (3%). Multivariate logistic regression analysis showed significant associations between use of sedatives and age (OR = 0.94, P < .001) as well as institution (P < .001). CONCLUSIONS AND IMPLICATIONS: Our data indicate a lower prevalence of sedation compared to international data and considerable differences regarding prevalence between institutions. These differences, potential setting-specific challenges, and need for support measures for consistent best practice of sedation in nursing homes should be further explored.

Next Generation of Zinc Bisguanidine Polymerization Catalysts towards Highly Crystalline, Biodegradable Polyesters.

Polylactide and polycaprolactone are both biodegradable polymers produced through metal-catalyzed ring-opening polymerization. For a truly sustainable lifecycle of these polymers it is essential to replace the industrially used cytotoxic catalyst tin(II) bis(2-ethylhexanoate) [Sn(Oct)2 ] with non-toxic alternatives. Here, we report the fastest known robust catalyst in the polymerization of lactide and ϵ-caprolactone. This zinc guanidine catalyst can polymerize non-purified technical rac-lactide and ϵ-caprolactone in the melt at different [M]/[I] ratios with fast rate constants, high molar masses, and high yields in a short time, leading to colorless, transparent polymer. Moreover, we report that polylactide and polycaprolactone produced by zinc-guanidine complexes have favorably high crystallinities. In fact, the obtained polylactide shows a more robust degradation profile than its Sn(Oct)2 -catalysed equivalent due to a higher degree of crystallinity.

3D Heterocycles from Sulfonimidamides by Sequential C-H Bond Alkenylation/Aza-Michael Cyclization.

Starting from NH-sulfonimidamides, rhodium-catalyzed C-H bond alkenylation followed by aza-Michael cyclization leads to unprecedented benzoisothiazole 1-oxides. The applicability and robustness of the method is demonstrated in 25 examples with yields up to 95 %. The resulting scaffolds are partly saturated, 3D heterocycles with potential significance for medicinal and agricultural chemistry.

Tuning a robust system: N,O zinc guanidine catalysts for the ROP of lactide.

Non-toxic, highly active and robust complexes are the holy grail as ideal green catalysts for the polymerisation of biorenewable and biodegradable polylactide. Four new zinc guanidine complexes [ZnCl2(TMG4NMe2asme)], [ZnCl2(TMG5Clasme)], [ZnCl2(TMG5Measme)] and [ZnCl2(TMG5NMe2asme)] with different electron-donating and electron-withdrawing groups on the ligand's aromatic backbone have been synthesised. Ligands are derived from low-cost commercially available compounds and have been converted by a three- or four-step synthesis process into the desired ligand in good yields. The compounds have been fully characterised and tested in the ROP of rac-LA under industrially relevant conditions. The complexes are based on the recently published structure [ZnCl2(TMGasme)] which has shown high activity in the polymerisation of lactide at 150 °C. Different substituents in the para-position of the guanidine moiety significantly increase the polymerisation rate whereas positioning substituents in the meta-position causes no change in the reaction rate. With molecular weights over 71 000 g mol-1 being achievable, the best system produces polymers for multiple industrial applications and its polymerisation rate approaches that of Sn(Oct)2. The robust systems are able to polymerise non-purified lactide. The initiation of the polymerisation is suggested to occur due to impurities in the monomer.

Iron Oxide-labeled Collagen Scaffolds for Non-invasive MR Imaging in Tissue Engineering.

Non-invasive imaging holds significant potential for implementation in tissue engineering. It can e.g. be used to monitor the localization and function of tissue-engineered implants, as well as their resorption and remodelling. Thus far, however, the vast majority of efforts in this area of research have focused on the use of ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle-labeled cells, colonizing the scaffolds, to indirectly image the implant material. Reasoning that directly labeling scaffold materials might be more beneficial (enabling imaging also in case of non-cellularized implants), more informative (enabling the non-invasive visualization and quantification of scaffold degradation) and more easy to translate into the clinic (since cell-free materials are less complex from a regulatory point-of-view), we here prepared three different types of USPIO nanoparticles, and incorporated them both passively and actively (via chemical conjugation; during collagen crosslinking) into collagen-based scaffold materials. We furthermore optimized the amount of USPIO incorporated into the scaffolds, correlated the amount of entrapped USPIO with MR signal intensity, showed that the labeled scaffolds are highly biocompatible, demonstrated that scaffold degradation can be visualized using MRI and provided initial proof-of-principle for the in vivo visualization of the scaffolds. Consequently, USPIO-labeled scaffold materials seem to be highly suitable for image-guided tissue engineering applications.