Relationship between Composition and Environmental Degradation of Poly(isosorbide-co-diol oxalate) (PISOX) Copolyesters.

To reduce the global CO2 footprint of plastics, bio- and CO2-based feedstock are considered the most important design features for plastics. Oxalic acid from CO2 and isosorbide from biomass are interesting rigid building blocks for high Tg polyesters. The biodegradability of a family of novel fully renewable (bio- and CO2-based) poly(isosorbide-co-diol) oxalate (PISOX-diol) copolyesters was studied. We systematically investigated the effects of the composition on biodegradation at ambient temperature in soil for PISOX (co)polyesters. Results show that the lag phase of PISOX (co)polyester biodegradation varies from 0 to 7 weeks. All (co)polyesters undergo over 80% mineralization within 180 days (faster than the cellulose reference) except one composition with the cyclic codiol 1,4-cyclohexanedimethanol (CHDM). Their relatively fast degradability is independent of the type of noncyclic codiol and results from facile nonenzymatic hydrolysis of oxalate ester bonds (especially oxalate isosorbide bonds), which mostly hydrolyzed completely within 180 days. On the other hand, partially replacing oxalate with terephthalate units enhances the polymer's resistance to hydrolysis and its biodegradability in soil. Our study demonstrates the potential for tuning PISOX copolyester structures to design biodegradable plastics with improved thermal, mechanical, and barrier properties.

Ultra-Tough Elastomers from Stereochemistry-Directed Hydrogen Bonding in Isosorbide-Based Polymers.

The remarkable elasticity and tensile strength found in natural elastomers are challenging to mimic. Synthetic elastomers typically feature covalently cross-linked networks (rubbers), but this hinders their reprocessability. Physical cross-linking via hydrogen bonding or ordered crystallite domains can afford reprocessable elastomers, but often at the cost of performance. Herein, we report the synthesis of ultra-tough, reprocessable elastomers based on linear alternating polymers. The incorporation of a rigid isohexide adjacent to urethane moieties affords elastomers with exceptional strain hardening, strain rate dependent behavior, and high optical clarity. Distinct differences were observed between isomannide and isosorbide-based elastomers where the latter displays superior tensile strength and strain recovery. These phenomena are attributed to the regiochemical irregularities in the polymers arising from their distinct stereochemistry and respective inter-chain hydrogen bonding.

Isosorbide plasticized corn starch filled with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) microparticles: Properties and behavior under environmental factors.

In this work, new green and fully biodegradable composites, based on corn starch, plasticized with two different amounts of isosorbide and filled by poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microparticles, were obtained by melt processing. The analysis of their morphologies, crystallinity, structural interactions and dynamomechanical properties as well as the evaluation of their moisture resistance and biodegradability in soil, were performed in function of the plasticizer and/or microparticle amount. The analysis of morphology, crystallinity and structural interactions showed that the plasticization process was completed under the melting processing conditions used. The microparticles were homogeneously dispersed in the thermoplastic starch matrix without suffering any deformation or breaking during the processing. Biocomposites with adequate storage modulus values were obtained, especially the TPS plasticized with 35% of isosorbide and filled with 5 wt% of PHBV microparticles. The incorporation of PHBV microparticles leads to biocomposites with higher moisture resistance. All the biocomposites were completely biodegraded in soil in a short period of time. The performed study demonstrated that these biocomposites could be used for applications in the packaging industry.

Isosorbide Di-(Linoleate/Oleate) Stimulates Prodifferentiation Gene Expression to Restore the Epidermal Barrier and Improve Skin Hydration.

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin.

Biosourced All-Acrylic ABA Block Copolymers with Lactic Acid-Based Soft Phase.

Lactic acid is one of the key biobased chemical building blocks, given its readily availability from sugars through fermentation and facile conversion into a range of important chemical intermediates and polymers. Herein, well-defined rubbery polymers derived from butyl lactate solvent were successfully prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of the corresponding monomeric acrylic derivative. Good control over molecular weight and molecular weight distribution was achieved in bulk using either monofunctional or bifunctional trithiocarbonate-type chain transfer agents. Subsequently, poly(butyl lactate acrylate), with a relative low Tg (-20 °C), good thermal stability (5% wt. loss at 340 °C) and low toxicity was evaluated as a sustainable middle block in all-acrylic ABA copolymers using isosorbide and vanillin-derived glassy polyacrylates as representative end blocks. Thermal, morphological and mechanical properties of copolymers containing hard segment contents of <20 wt% were evaluated to demonstrate the suitability of rubbery poly(alkyl lactate) building blocks for developing functional sustainable materials. Noteworthy, 180° peel adhesion measurements showed that the synthesized biosourced all-acrylic ABA copolymers possess competitive performance when compared with commercial pressure-sensitive tapes.

Properties and behavior under environmental factors of isosorbide-plasticized starch reinforced with microcrystalline cellulose biocomposites.

Green biocomposites based on corn starch plasticized with isosorbide and glycerol and filled with microcrystalline cellulose (MCC) were processed. The structural interactions, dynamomechanical properties, water absorption, and soil biodegradability were investigated by different techniques considering the effect of the type and amount of plasticizer and the MCC addition. The changes along the time of the structural interactions and the dynamomechanical properties of these materials and the influence of the retrogradation phenomenon were also studied. The use of isosorbide as plasticizer instead of glycerol improved the stiffness, the water absorption and the biodegradation rate of thermoplastic starch (TPS). Moreover, no evidence of retrogradation for isosorbide was observed. An isosorbide content of 35% and the addition of MCC filler enhanced in a greater extent these properties with a complete biodegradability in 7 month. These green biocomposites can be an alternative for food packaging applications.

Computer-based formulation design and optimization using Hansen solubility parameters to enhance the delivery of ibuprofen through the skin.

Trial-and-error approach to formulation development is long and costly. With growing time and cost pressures in the pharmaceutical industry, the need for computer-based formulation design is greater than ever. In this project, emulgels were designed and optimized using Formulating for Efficacy™ (FFE) for the topical delivery of ibuprofen. FFE helped select penetration enhancers, design and optimize emulgels and simulate skin penetration studies. pH, viscosity, spreadability, droplet size and stability of emulgels were evaluated. Franz cell studies were performed to test in vitro drug release on regenerated cellulose membrane, drug permeation in vitro on Strat-M® membrane and ex vivo on porcine ear skin, a marketed ibuprofen gel served as control. Emulgels had skin compatible pH, viscosity and spreadability comparable to a marketed emulgel, were opaque and stable at 25 °C for 6 months. Oleyl alcohol (OA), combined with either dimethyl isosorbide (DMI) or diethylene glycol monoethyl ether (DGME) provided the highest permeation in 24 h in vitro, which was significantly higher than the marketed product (p < 0.01). OA + DGME significantly outperformed OA ex vivo (p < 0.05). The computer predictions, in vitro and ex vivo penetration results correlated well. FFE was a fast, valuable and reliable tool for aiding in topical product design for ibuprofen.

Study on the Synthetic Characteristics of Biomass-Derived Isosorbide-Based Poly(arylene ether ketone)s for Sustainable Super Engineering Plastic.

Demand for the development of novel polymers derived from biomass that can replace petroleum resources has been increasing. In this study, biomass-derived isosorbide was used as a monomer in the polymerization of poly(arylene ether ketone)s, and its synthetic characteristics were investigated. As a phase-transfer catalyst, crown ether has increased the weight-average molecular weight of polymers over 100 kg/mol by improving the reaction efficiency of isosorbide and minimizing the effect of moisture. By controlling the experimental parameters such as halogen monomer, polymerization solvent, time, and temperature, the optimal conditions were found to be fluorine-type monomer, dimethyl sulfoxide, 24 h, and 155 °C, respectively. Biomass contents from isosorbide-based polymers were determined by nuclear magnetic resonance and accelerator mass spectroscopy. The synthesized polymer resulted in a high molecular weight that enabled the preparation of transparent polymer films by the solution casting method despite its weak thermal degradation stability compared to aromatic polysulfone. The melt injection molding process was enabled by the addition of plasticizer. The tensile properties were comparable or superior to those of commercial petrochemical specimens of similar molecular weight. Interestingly, the prepared specimens exhibited a significantly lower coefficient of thermal expansion at high temperatures over 150 °C compared to polysulfone.

Ultrasound-Assisted Heterogeneous Synthesis of Bio-Based Oligo-Isosorbide Glycidyl Ethers: Towards Greener Epoxy Precursors.

The substitution of toxic precursors such as bisphenol A by renewable and safer molecules has become a major challenge. To overcome this challenge, the 12 principles of green chemistry should be taken into account in the development of future sustainable chemicals and processes. In this context, this paper reports the highly efficient synthesis of oligo-isosorbide glycidyl ethers from bio-based starting materials by a rapid one-pot heterogeneous ultrasound-assisted synthesis. It was demonstrated that the use of high-power ultrasound in solvent-free conditions with sodium hydroxide microbeads led for the first time to a fully epoxidated prepolymer with excellent epoxy equivalent weight (EEW). The structure of the epoxy precursor was characterized by FT-IR, NMR spectroscopy and high-resolution mass spectrometry (HRMS). The efficiency of the ultrasound-assisted synthesis was attributed to the physical effects caused by micro-jets on the surface of the solid sodium hydroxide microspheres following the asymmetrical collapse of cavitation bubbles.

Effects of Isosorbide Incorporation into Flexible Polyurethane Foams: Reversible Urethane Linkages and Antioxidant Activity.

Isosorbide (ISB), a nontoxic bio-based bicyclic diol composed from two fuzed furans, was incorporated into the preparation of flexible polyurethane foams (FPUFs) for use as a cell opener and to impart antioxidant properties to the resulting foam. A novel method for cell opening was designed based on the anticipated reversibility of the urethane linkages formed by ISB with isocyanate. FPUFs containing various amounts of ISB (up to 5 wt%) were successfully prepared without any noticeable deterioration in the appearance and physical properties of the resulting foams. The air permeability of these resulting FPUFs was increased and this could be further improved by thermal treatment at 160 °C. The urethane units based on ISB enabled cell window opening, as anticipated, through the reversible urethane linkage. The ISB-containing FPUFs also demonstrated better antioxidant activity by impeding discoloration. Thus, ISB, a nontoxic, bio-based diol, can be a valuable raw material (or additive) for eco-friendly FPUFs without seriously compromising the physical properties of these FPUFs.

Preparation and Characterization of Isosorbide-Based Self-Healable Polyurethane Elastomers with Thermally Reversible Bonds.

Polyurethane (PU) is a versatile polymer used in a wide range of applications. Recently, imparting PU with self-healing properties has attracted much interest to improve the product durability. The self-healing mechanism conceivably occurs through the existence of dynamic reversible bonds over a specific temperature range. The present study investigates the self-healing properties of 1,4:3,6-dianhydrohexitol-based PUs prepared from a prepolymer of poly(tetra-methylene ether glycol) and 4,4'-methylenebis(phenyl isocyanate) with different chain extenders (isosorbide or isomannide). PU with the conventional chain extender 1,4-butanediol was prepared for comparison. The urethane bonds in 1,4:3,6-dianhydrohexitol-based PUs were thermally reversible (as confirmed by the generation of isocyanate peaks observed by Fourier transform infrared spectroscopy) at mildly elevated temperatures and the PUs showed good mechanical properties. Especially the isosorbide-based polyurethane showed potential self-healing ability under mild heat treatment, as observed in reprocessing tests. It is inferred that isosorbide, bio-based bicyclic diol, can be employed as an efficient chain extender of polyurethane prepolymers to improve self-healing properties of polyurethane elastomers via reversible features of the urethane bonds.

Catastrophic Emulsion Inversion Process of Highly Viscous Isosorbide Biobased Polyester Monitoredin situ by Torque and Light Backscattering.

Highly viscous hydrophobic isosorbide biobased polyester O/W emulsions are prepared through catastrophic phase inversion. The process is followed in situ with two different methods: torque and light backscattering (LBS). Considering high viscosity of the system, only discontinuous conductivity monitoring is performed for comparison. Torque and LBS allow to highlight the emulsion inversion point (EIP) with relatively close water weight fraction values (fw≈0.20). The torque and LBS signals are rather noisy before inversion (evolution of different structures) and more smooth after phase inversion (continuous aqueous phase). Torque gives a more macroscopic information, representative of the global state of the dispersion. Consistent conductivity and torque measurements suggest indeed an inversion pathway through multiple o/W/O emulsions leading to multiple complex structures before getting continuous aqueous final emulsion. This hypothesis is confirmed with continuous LBS monitoring and microscopic observations. LBS signal seems more complete because it combines the information of conductivity and torque and allows to clearly follow in situ the inversion from the beginning to the end of the process.

Isosorbide as Core Component for Tailoring Biobased Unsaturated Polyester Thermosets for a Wide Structure-Property Window.

Biobased unsaturated polyester thermosets as potential replacements for petroleum-based thermosets were designed. The target of incorporating rigid units, to yield thermosets with high thermal and mechanical performance, both in the biobased unsaturated polyester (UP) and reactive diluent (RD) while retaining miscibility was successfully achieved. The biobased unsaturated polyester thermosets were prepared by varying the content of isosorbide, 1,4-butanediol, maleic anhydride, and succinic anhydride in combination with the reactive diluent isosorbide-methacrylate (IM). Isosorbide was chosen as the main component in both the UP and the RD to enhance the rigidity of the formed thermosets, to overcome solubility issues commonly associated with biobased UPs and RDs and volatility and toxicity associated with styrene as RD. All UPs had good solubility in the RD and the viscosity of the mixtures was primarily tuned by the feed ratio of isosorbide but also by the amount of maleic anhydride. The flexural modulus and storage modulus were tailorable by altering the monomer composition The fabricated thermosets had superior thermal and mechanical properties compared to most biobased UP thermosets with thermal stability up to about 250 °C and a storage modulus at 25 °C varying between 0.5 and 3.0 GPa. These values are close to commercial petroleum-based UP thermosets. The designed tailorable biobased thermosets are, thus, promising candidates to replace their petroleum analogs.

Isosorbide-based peptidomimetics as inhibitors of hepatitis C virus serine protease.

Hepatitis C infection is a cause of chronic liver diseases such as cirrhosis and carcinoma. The current therapy for hepatitis C has limited efficacy and low tolerance. The HCV encodes a serine protease which is critical for viral replication, and few protease inhibitors are currently on the market. In this paper, we describe the synthesis and screening of novel isosorbide-based peptidomimetic inhibitors, in which the compounds 1d, 1e, and 1i showed significant inhibition of the protease activity in vitro at 100µM. The compound 1e also showed dose-response (IC50=36±3µM) and inhibited the protease mutants D168A and V170A at 100µM, indicating it as a promising inhibitor of the HCV NS3/4A protease. Our molecular modeling studies suggest that the activity of 1e is associated with a change in the interactions of S2 and S4 subsites, since that the increased flexibility favors a decrease in activity against D168A, whereas the appearance of a hydrophobic cavity in the S4 subsite increase the inhibition against V170A strain.

One-Pot Preparation of Dimethyl Isosorbide from d-Sorbitol via Dimethyl Carbonate Chemistry.

Direct synthesis of dimethyl isosorbide (DMI) from d-sorbitol via dimethyl carbonate (DMC) chemistry is herein first reported. High yield of DMI was achieved using the nitrogen superbase 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst and performing the reaction in a stainless steel autoclave by increasing the temperature from 90 to 200 °C. In this procedure, DMC features its full capacity acting in the different steps of the process as carboxymethylating, leaving-group (cyclization), and methylating agent; DMC is also employed as the reaction media.

Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the stratum corneum.

Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using hens egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.

Synthesis of 2-[(18)F]Fluoro-2-deoxyisosorbide 5-mononitrate and Assessment of Its in vivo Biodistribution as Determined by Dynamic Positron Emission Tomography (PET).

Herein we disclose the synthesis of 2-fluoro-2-deoxyisosorbide 5-mononitrate (2F-IS-5MN), a fluorinated analogue of the commonly prescribed vasodilator isosorbide 5-mononitrate (IS-5MN). X-ray structural data for IS-5MN and its C2-epimeric congener IM-5MN are presented together with structural data for 2F-IS-5MN. Radioisotope labeling of 2F-IS-5MN has, for the first time, allowed observation of the in vivo biodistribution of this organic nitrate by means of dynamic positron emission tomography (PET) in wild-type mice.

Synthesis of bio-based thermoplastic polyurethane elastomers containing isosorbide and polycarbonate diol and their biocompatible properties.

A new family of highly elastic polyurethanes (PUs) partially based on renewable isosorbide were prepared by reacting hexamethylene diisocyanate with a various ratios of isosorbide and polycarbonate diol 2000 (PCD) via a one-step bulk condensation polymerization without catalyst. The influence of the isorsorbide/PCD ratio on the properties of the PU was evaluated. The successful synthesis of the PUs was confirmed by Fourier transform-infrared spectroscopy and (1)H nuclear magnetic resonance. The resulting PUs showed high number-average molecular weights ranging from 56,320 to 126,000 g mol(-1) and tunable Tg values from -34 to -38℃. The thermal properties were determined by differential scanning calorimetry and thermogravimetric analysis. The PU films were flexible with breaking strains from 955% to 1795% at from 13.5 to 54.2 MPa tensile stress. All the PUs had 0.9-2.8% weight lost over 4 weeks and continual slow weight loss of 1.1-3.6% was observed within 8 weeks. Although the cells showed a slight lower rate of proliferation than that of the tissue culture polystyrene as a control, the PU films were considered to be cytocompatible and nontoxic. These thermoplastic PUs were soft, flexible and biocompatible polymers, which open up a range of opportunities for soft tissue augmentation and regeneration.

Unexpected tackifiers from isosorbide.

Molecularly well-defined tackifiers with up to 100 % bio-content were prepared from isosorbide and various cyclic anhydrides. These tackifiers are tacky over a broad temperature range and exhibit high maximum tack (ca. 2000 kPa). Structural modifications shift the temperature at which maximum tack is observed and change the viscosity of the tackifiers.

Isosorbide, a green plasticizer for thermoplastic starch that does not retrogradate.

Isosorbide is a non-toxic biodegradable diol derived from bio-based feedstock. It can be used for preparing thermoplastic starch through a semi-industrial process of extrusion. Isosorbide allows some technological advantages with respect to classical plasticizers: namely, direct mixing with starch, energy savings for the low processing temperature required and lower water uptake. Indeed, maize starch was directly mixed with the solid plasticizer and direct fed in the main hopper of a co-rotating twin screw extruder. Starch plasticization was assessed by X-ray diffraction (XRD) and dynamic-mechanical analysis (DMTA). Oxygen permeability, water uptake and mechanical properties were measured at different relative humidity (R.H.) values. These three properties turned out to be highly depending on the R.H. No retrogradation and changing of the material properties were occurred from XRD and DMTA after 9 months.