Sustainable Procedures for Cellulose Derivatizations and Renewable Thermoset Materials

Synthetische Polymere haben aufgrund ihrer in vielerlei Hinsicht attraktiven Materialeigenschaften sowie ihrer kostengünstigen Herstellung in den letzten Jahrzehnten unser tägliches Leben grundlegend verändert. Die meisten dieser Polymere basieren jedoch vollständig auf Erdöl und ihre Herstellung kann aufgrund der Erschöpfung dieser fossilen Ressourcen und weiterer Aspekte nicht als nachhaltig angesehen werden. Die Nutzung nachwachsender Rohstoffe für die Polymersynthese ist daher inzwischen von besonderem Interesse. Gleichzeitig müssen mehrere weitere Aspekte für die Gestaltung nachhaltigerer Synthesewege berücksichtigt werden, wie die Vermeidung von Abfallprodukten, die Verwendung von unbedenklichen Reagenzien und die Reduzierung von Hilfsstoffen (z. B. Lösungsmitteln). In diesem Zusammenhang wurden die zwölf Prinzipien der grünen Chemie verfasst, welche in dieser Arbeit als Leitlinien für die Entwicklung neuartiger Verfahren zur Synthese polymerer Materialien auf Basis nachwachsender Rohstoffe dienen. Zunächst wurde ein neuartiges Cellulose Acetylierungsverfahren unter Nutzung des DMSO/DBU/CO2 schaltbaren Lösungsmittelsystems ohne die Notwendigkeit eines zusätzlichen Katalysators oder Aktivierungsschrittes entwickelt. Vinylacetat wurde als umweltfreundlicheres Acetylierungsmittel unter milden Bedingungen verwendet, und ein einfaches Recycling aller verwendeten Komponenten wurde mit hohen Recyclingquoten (87,0–98,9%) gezeigt. Im Vergleich zum industriell angewandten heterogenen Eisessigverfahren wurde ein geringerer Abbau des Celluloserückgrats aufgrund der nicht-sauren Bedingungen festgestellt (Mn = 35 kDa vs. 12 kDa). Eine direkte Synthese von Celluloseacetaten mit niedrigeren Substitutionsgraden aufgrund der homogenen Bedingungen konnte durch einfaches Anpassen der Äquivalente an Acetylierungsmittel ermöglicht werden. Mit Bezug hierzu wurde eine neue Methode zur Bestimmung des Substitutionsgrades von Celluloseacetaten, -butyraten, -lauraten und -benzoaten mittels ATR-FTIR-Spektroskopie unter Anwendung eines neuartigen nichtlinearen Korrelationsansatzes etabliert. Das DMSO/DBU/CO2 schaltbare Lösungsmittel wurde des Weiteren zur Entwicklung eines Tandem-Reaktionsansatz zur Cellulose-Derivatisierung genutzt, der einen einzigen Katalysator für drei aufeinanderfolgende Umwandlungen verwendet. Bei diesem Verfahren wurde Cellulose zunächst gelöst und dann mit vier verschiedenen Isothiocyanaten funktionalisiert, die in situ über eine katalytische Sulfurierung von Isocyaniden mit elementarem Schwefel gebildet wurden. Dieses Eintopfverfahren erwies sich hinsichtlich Effizienz und Nachhaltigkeit als vorteilhaft gegenüber einer schrittweisen Synthese und ermöglichte Recyclingquoten der eingesetzten Komponenten von 79,1 bis 95,6%. Durch Erweiterung dieses Ansatzes auf Rizinusöl als natürliches Polyol wurden neuartige Thionourethan-Duroplaste synthetisiert. Ähnlich wie beim vorherigen Ansatz für die Cellulosefunktionalisierung wurden die funktionellen Isothiocyanatgruppen in situ über eine katalytische Sulfurierung von Isocyaniden mit elementarem Schwefel erzeugt, jedoch bei diesem Ansatz ohne die Notwendigkeit eines zusätzlichen Lösungsmittels. Es wurde festgestellt, dass Rizinusöl als Lösungsmittel für die Isothiocyanatbildung fungiert und anschließend als Polyolkomponente in der Thionourethan-Duroplastbildung vollständig reagiert. Die Kinetik dieser beiden Schritte wurde im Detail durch Echtzeit-IR-Messungen untersucht, und es wurde festgestellt, dass der Duroplast-Vernetzungsschritt thermisch auslösbar ist, nachdem das Diisothiocyanat quantitativ gebildet wurde, was eine hohe Kontrolle über den Aushärtungsprozess des Systems ermöglicht

Molecular data storage with zero synthetic effort and simple read-out

Compound mixtures represent an alternative, additional approach to DNA and synthetic sequence-defined macromolecules in the field of non-conventional molecular data storage, which may be useful depending on the target application. Here, we report a fast and efficient method for information storage in molecular mixtures by the direct use of commercially available chemicals and thus, zero synthetic steps need to be performed. As a proof of principle, a binary coding language is used for encoding words in ASCII or black and white pixels of a bitmap. This way, we stored a 25 × 25-pixel QR code (625 bits) and a picture of the same size. Decoding of the written information is achieved via spectroscopic (1H NMR) or chromatographic (gas chromatography) analysis. In addition, for a faster and automated read-out of the data, we developed a decoding software, which also orders the data sets according to an internal “ordering” standard. Molecular keys or anticounterfeiting are possible areas of application for information-containing compound mixtures

Determination of the degree of substitution of cellulose esters via ATR‐FTIR spectroscopy

Cellulose derivatives are promising bio-based polymeric materials with possible applications ranging from thickening agents and stabilizers to optical films. The precise determination of their degree of substitution (DS) is crucial, as the DS substantially influences the material properties of such cellulose derivatives. Herein, the applicability of attenuated total reflection-Fourier transform infrared for DS determination of cellulose esters was investigated. Sixteen cellulose acetates with DS ranging from 0.41 to 2.99 were synthesized and three acetyl group-specific vibrational signals were evaluated quantitatively in reference to the cellulose anhydroglucose unit vibration ν(C-O)$_{AGU}$. A non-linear correlation for the absorbance intensity with the DS was observed and the data was fitted based on a newly developed model with correlation coefficients R$^2$ between 0.958 and 0.998, depending on the evaluated signal. This DS determination method is simple and efficient, since it does not need any prederivatization or extensive sample preparation and can furthermore be applied to non-soluble samples. In order to widen the scope, eight cellulose butyrates, six cellulose laurates and six cellulose benzoates with different DS were synthesized and the DS determination method could be analogously applied to these cellulose esters, but a separate calibration for the different esters was found to be necessary

Advances and challenges in modeling inherited peripheral neuropathies using iPSCs

Inherited peripheral neuropathies (IPNs) are a group of diseases associated with mutations in various genes with fundamental roles in the development and function of peripheral nerves. Over the past 10 years, significant advances in identifying molecular disease mechanisms underlying axonal and myelin degeneration, acquired from cellular biology studies and transgenic fly and rodent models, have facilitated the development of promising treatment strategies. However, no clinical treatment has emerged to date. This lack of treatment highlights the urgent need for more biologically and clinically relevant models recapitulating IPNs. For both neurodevelopmental and neurodegenerative diseases, patient-specific induced pluripotent stem cells (iPSCs) are a particularly powerful platform for disease modeling and preclinical studies. In this review, we provide an update on different in vitro human cellular IPN models, including traditional two-dimensional monoculture iPSC derivatives, and recent advances in more complex human iPSC-based systems using microfluidic chips, organoids, and assembloids

Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination

Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process

Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 individuals of European ancestry and 6,784 individuals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a highly heritable disease (h2 = 0.42 ± 0.09). Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG ris

A more sustainable synthesis approach for cellulose acetate using the DBU/CO2_{2} switchable solvent system

Cellulose acetate is one of the most important cellulose derivatives and commercially mainly produced using the Acetic Acid Process, in which overstoichiometric amounts of acetic anhydride and concentrated acetic acid are used to obtain cellulose triacetate. A subsequent partial hydrolysis is necessary to achieve evenly substituted cellulose acetates with lower degrees of substitution. Homogeneous acetylations in ionic liquids or other cellulose dissolving solvent systems often offer milder conditions and the possibility of a one-step synthesis of cellulose acetates with lower degrees of substitution by simply adjusting the equivalents of the acetylation agent. Here, we show an efficient homogeneous cellulose acetylation process without the need of any additional catalyst or activation step using the DBU/CO$_{2}$ switchable solvent system. Vinyl acetate was used as a more benign acetylation agent under mild conditions and straightforward recyclability of all employed components was demonstrated with high recycling ratios (87.0–98.9%). Less cellulose backbone degradation compared to a cellulose acetate sample synthesized by the Acetic Acid Process from the same cellulose source was shown by size exclusion chromatography (M$_{n}$ = 35 kDa vs. 12 kDa), which resulted in improved mechanical properties of solvent casted foils. Other homogeneous procedures reported so far (e.g. in ionic liquids) reached lower degrees of substitution, needed additional catalysts, proved to be less advantageous in terms of recycling, or required more reactive acetylation agents. Our results thus demonstrate a cellulose acetylation method with full focus on sustainability, efficiency, and applicability, resulting in an E-factor of 1.92 for the overall process