An expeditive and green chemo-enzymatic route to diester sinapoyl-l-malate analogues: sustainable bioinspired and biosourced UV filters and molecular heaters.

Sinapoyl malate, naturally present in plants, has proved to be an exceptional UV filter and molecular heater for plants. Although there are nowadays industrially relevant sustainable synthetic routes to sinapoyl malate, its incorporation into certain cosmetic formulations, as well as its adsorption on plant leaves, is limited by its hydrophilicity. To overcome these obstacles, it is important to find a way to effectively control the hydrophilic-lipophilic balance of sinapoyl malate to make it readily compatible with the cosmetic formulations and stick on the waxy cuticle of leaves. To this end, herein, we describe a highly regioselective chemo-enzymatic synthesis of sinapoyl malate analogues possessing fatty aliphatic chains of variable length, enabling the lipophilicity of the compounds to be modulated. The potential toxicity (i.e., mutagenicity, carcinogenicity, endocrine disruption, acute and repeated-dose toxicity), bioaccumulation, persistence and biodegradability potential of these new analogues were evaluated in silico, along with the study of their transient absorption spectroscopy, their photostability as well as their photodegradation products.

Insight into the Photodynamics of Photostabilizer Molecules.

Solar exposure of avobenzone, one of the most widely used commercial UVA filters on the market, is known to cause significant degradation. This finding has fueled research into developing photostabilizer molecules. In an effort to provide insight into their stand-alone photoprotection properties, the excited state dynamics of the photostabilizer, 3-(3,4,5-trimethoxybenzylidene) pentane-2,4-dione (TMBP), and its phenolic derivative, 3-(4-hydroxy-3,5-dimethoxybenzylidene) pentane-2,4-dione (DMBP), were studied with ultrafast transient absorption spectroscopy. Solutions of TMPB and DMBP in ethanol and in an industry-standard emollient, as well as TMBP and DMBP deposited on synthetic skin mimic, were investigated. These experiments were allied with computational methods to aid interpretation of the experimental data. Upon photoexcitation, these photostabilizers repopulate the electronic ground state via nonradiative decay within a few picoseconds involving a twisted intramolecular charge transfer configuration in the excited state, followed by internal conversion and subsequent vibrational cooling in the ground state. This finding implies that, aside from acting as a photostabilizer to certain UV filters, TMBP and DMBP may offer additional photoprotection in a sunscreen formulation as a stand-alone UV filter. Finally, TMBP and DMBP could also find applications as molecular photon-to-heat converters.

From Biomass-Derived p-Hydroxycinnamic Acids to Novel Sustainable and Non-Toxic Phenolics-Based UV-Filters: A Multidisciplinary Journey.

Although organic UV-filters are extensively used in cosmetics to protect consumers from the deleterious effects of solar UV radiation-exposure, they suffer from some major drawbacks such as their fossil origin and their toxicity to both humans and the environment. Thus, finding sustainable and non-toxic UV-filters is becoming a topic of great interest for the cosmetic industry. A few years ago, sinapoyl malate was shown to be a powerful naturally occurring UV-filter. Building on these findings, we decided to design and optimize an entire value chain that goes from biomass to innovative biobased and non-toxic lignin-derived UV-filters. This multidisciplinary approach relies on: 1) The production of phenolic synthons using either metabolite extraction from biomass or their bioproduction through synthetic biology/fermentation/in stream product recovery; 2) their functionalization using green chemistry to access sinapoyl malate and analogues; 3) the study of their UV-filtering activity, their photostability, their biological properties; and 4) their photodynamics. This mini-review aims at demonstrating that combining biotechnology, green chemistry, downstream process and photochemistry is a powerful approach to transform biomass and, in particular lignins, into high value-added innovative UV-filters.

Blending Ferulic Acid Derivatives and Polylactic Acid into Biobased and Transparent Elastomeric Materials with Shape Memory Properties.

Thanks to its remarkable properties such as sustainability, compostability, biocompatibility, and transparency, poly-l-lactic acid (PLA) would be a suitable replacement for oil-based polymers should it not suffer from low flexibility and poor toughness, restricting its use to rigid plastic by excluding elastomeric applications. Indeed, there are few fully biobased and biodegradable transparent elastomers-PLA-based or not-currently available. In the last decades, many strategies have been investigated to soften PLA and enhance its toughness and elongation at break by using plasticizers, oligomers, or polymers. This work shows how a ferulic acid-derived biobased additive (BDF) blends with a common rigid and brittle commercial grade of polylactic acid to provide a transparent non-covalently cross-linked elastomeric material with shape memory behavior exhibiting an elongation at break of 434% (vs 6% for pristine PLA). Through a structure-activity relationship analysis conducted with BDF analogues and a modeling study, we propose a mechanism based on π-π stacking to account for the elastomeric properties. Blending ferulic acid derivatives with polylactic acid generates a new family of fully sustainable transparent elastomeric materials with functional properties such as shape memory.

Towards developing novel and sustainable molecular light-to-heat converters.

Light-to-heat conversion materials generate great interest due to their widespread applications, notable exemplars being solar energy harvesting and photoprotection. Another more recently identified potential application for such materials is in molecular heaters for agriculture, whose function is to protect crops from extreme cold weather and extend both the growing season and the geographic areas capable of supporting growth, all of which could help reduce food security challenges. To address this demand, a new series of phenolic-based barbituric absorbers of ultraviolet (UV) radiation has been designed and synthesised in a sustainable manner. The photophysics of these molecules has been studied in solution using femtosecond transient electronic and vibrational absorption spectroscopies, allied with computational simulations and their potential toxicity assessed by in silico studies. Following photoexcitation to the lowest singlet excited state, these barbituric absorbers repopulate the electronic ground state with high fidelity on an ultrafast time scale (within a few picoseconds). The energy relaxation pathway includes a twisted intramolecular charge-transfer state as the system evolves out of the Franck-Condon region, internal conversion to the ground electronic state, and subsequent vibrational cooling. These barbituric absorbers display promising light-to-heat conversion capabilities, are predicted to be non-toxic, and demand further study within neighbouring application-based fields.

New Generation UV-A Filters: Understanding Their Photodynamics on a Human Skin Mimic.

The sparsity of efficient commercial ultraviolet-A (UV-A) filters is a major challenge toward developing effective broadband sunscreens with minimal human- and eco-toxicity. To combat this, we have designed a new class of Meldrum-based phenolic UV-A filters. We explore the ultrafast photodynamics of coumaryl Meldrum, CMe, and sinapyl Meldrum (SMe), both in an industry-standard emollient and on a synthetic skin mimic, using femtosecond transient electronic and vibrational absorption spectroscopies and computational simulations. Upon photoexcitation to the lowest excited singlet state (S1), these Meldrum-based phenolics undergo fast and efficient nonradiative decay to repopulate the electronic ground state (S0). We propose an initial ultrafast twisted intramolecular charge-transfer mechanism as these systems evolve out of the Franck-Condon region toward an S1/S0 conical intersection, followed by internal conversion to S0 and subsequent vibrational cooling. Importantly, we correlate these findings to their long-term photostability upon irradiation with a solar simulator and conclude that these molecules surpass the basic requirements of an industry-standard UV filter.

Exploring the Photochemistry of an Ethyl Sinapate Dimer: An Attempt Toward a Better Ultraviolet Filter.

The photochemistry and photostability of a potential ultraviolet (UV) radiation filter, dehydrodiethylsinapate, with a broad absorption in the UVA region, is explored utilizing a combination of femtosecond time-resolved spectroscopy and steady-state irradiation studies. The time-resolved measurements show that this UV filter candidate undergoes excited state relaxation after UV absorption on a timescale of ~10 picoseconds, suggesting efficient relaxation. However, steady-state irradiation measurements show degradation under prolonged UV exposure. From a photochemical standpoint, this highlights the importance of considering both the ultrafast and "ultraslow" timescales when designing new potential UV filters.

Sinapic Acid Esters: Octinoxate Substitutes Combining Suitable UV Protection and Antioxidant Activity.

In 2021, Hawaii will permanently ban the use and sale of octinoxate-based sunscreens as studies have shown serious impacts of such UV filters on the coral reef. This ban, which could be generalized to other countries, highlights the extreme need to offer alternative UV filters that are not only effective in terms of sun protection, but also healthy with regards to human health and the environment. In this context, a wide library of p-hydroxycinnamic esters deriving from naturally occurring sinapic acid has been synthesized using a Knoevenagel-Doebner condensation. The UV filtering activities as well as the antioxidant properties of these sinapic acid esters were then investigated. The results showed promising UVB protection and antioxidant efficacy. A Structure-Activity Relationship (SAR) study on the sinapic acid esters highlighted the need of a free phenol to, as expected, observe antioxidant activity, but also to obtain a higher intensity of protection. Moreover, the nature of the ester moiety also proved to be a key structural feature for the UV absorbance, as higher steric hindrance on the ester moiety leads to more active compounds. The judicious structural design of sinapic esters thus provides promising compounds combining UV protection and antioxidant activity.

Sustainable Straightforward Synthesis and Evaluation of the Antioxidant and Antimicrobial Activity of Sinapine and Analogues.

Naturally occurring sinapine was successfully synthesized through a proline-mediated Knoevenagel-Doebner condensation in ethanol. This synthetic process involving biobased syringaldehyde, Meldrum's acid, and choline chloride offers a sustainable alternative to the existing low-yield pathways. This two-step strategy gives access to sinapine in a 52% overall yield and has been implemented in the synthesis of sinapine analogues, using 4-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and vanillin as precursors, giving target molecules with 34-61% overall isolated yields. The purity of synthetic sinapine and its analogues (ca. 95%) was assessed by NMR and high-performance liquid chromatography-mass spectrometry analyses. Furthermore, the antioxidant and antimicrobial activities were assessed, and the potential of this series of molecules was confirmed.

Innovative Bio-Based Organic UV-A and Blue Light Filters from Meldrum's Acid.

Faced with the ban of some organic UV filters such as octinoxate or avobenzone, especially in Hawaii, it became essential to offer new alternatives that are both renewable and safe for humans and the environment. In this context, a class of bio-based molecules displaying interesting UV filter properties and great (photo)stability has been developed from Meldrum's acid and bio-based and synthetic p-hydroxycinnamic acids, furans and pyrroles. Moreover, p-hydroxycinnamic acid-based Meldrum's derivatives possess valuable secondary activities sought by the cosmetic industry such as antioxidant and anti-tyrosinase properties. The evaluation of the properties of mixture of judiciously chosen Meldrum's acid derivatives highlighted the possibility to modulate secondary activity while maintaining excellent UV protection. Meldrum's acid derivatives are not only competitive when benchmarked against organic filters currently on the market (i.e., avobenzone), but they also do not exhibit any endocrine disruption activity.

Sustainable Synthesis of p-Hydroxycinnamic Diacids through Proline-Mediated Knoevenagel Condensation in Ethanol: An Access to Potent Phenolic UV Filters and Radical Scavengers.

p-Hydroxycinnamic diacids are reaction intermediates of the classical Knoevenagel-Doebner condensation between malonic acid and benzaldehydes. As they are generally obtained in low yields, they remain relatively under-studied and under-exploited. Herein, we developed and optimized a sustainable synthetic procedure allowing the production of these compounds in good to high yields (60-80%) using proline as the catalyst and ethanol as the solvent. Study of their antioxidant and anti-UV activities revealed that these p-hydroxycinnamic diacids were not only potent radical scavengers but also efficient UV filters exhibiting high photostability.