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

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

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

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 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

Straightforward sustainable synthesis of novel non-endocrine disruptive bio-based organic UV-B filters with antimicrobial activity

ABSTRACTWith an increasing demand for safe and natural products from both industries and consumers, paired with the recent ban of decried molecules (i.e. octinoxate, avobenzone or octocrylene) due to their high negative impact on humans and the environment (i.e. endocrine disruption, coral bleaching), safe bio-based alternatives are a necessary and promising surrogate to substitute current commercialized petroleum-based UV filters. In this context, a class of bio-based molecules, displaying interesting UV-B filtering properties and great photostability were developed from furfural and 5-hydroxymethylfurfural (HMF), using the Knoevenagel condensation with a set of green conditions to minimize the impact on environment. Furthermore, those furfural- and HMF-based molecules demonstrated antimicrobial properties as secondary activity, highly sought by industries. Some furan derivatives being recognized to exhibit toxicological risks, in silico and in vitro assays were conducted and demonstrated the absence of endocrine disruption activity for these new molecules

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

Bio-based photo-reversible self-healing polymer designed from lignin

Lignocellulose-derived p-hydroxycinnamic acids possess the photo-responsive reversible α,β-unsaturated ester moiety, a reactive structural feature that functions as the basis of the photo-reversible [2 + 2] cycloaddition reaction. To explore the potential of these naturally occurring compounds in the field of self-healing materials, novel bio-based photo-crosslinkable lignin- and glycerol-derived polyfunctional monomers having cinnamate groups were produced using a sustainable process from vanillin and syringaldehyde, two compounds readily obtained from the oxidation of lignin. Through a Structure–Activity Relationship (SAR) study, the structural design of these bio-based monomers was optimized with regards to the crosslinking/decrosslinking extent and the self-healing capacity of the corresponding polymer material. The lignin- and glycerol-derived tri-functional monomer with 4-O-propyl-ferulate moieties has facilitated the design of a new family of bio-based, environment-friendly and reversible self-healing materials for widespread applications. Computational density-functional theory (DFT) and time-dependent DFT calculations were further used for the verification of the SAR study in terms of dimerization energy of the synthesized monomers

Straightforward sustainable synthesis of novel non-endocrine disruptive bio-based organic UV-B filters with antimicrobial activity

With an increasing demand for safe and natural products from both industries and consumers, paired with the recent ban of decried molecules (i.e. octinoxate, avobenzone or octocrylene) due to their high negative impact on humans and the environment (i.e. endocrine disruption, coral bleaching), safe bio-based alternatives are a necessary and promising surrogate to substitute current commercialized petroleum-based UV filters. In this context, a class of bio-based molecules, displaying interesting UV-B filtering properties and great photostability were developed from furfural and 5-hydroxymethylfurfural (HMF), using the Knoevenagel condensation with a set of green conditions to minimize the impact on environment. Furthermore, those furfural- and HMF-based molecules demonstrated antimicrobial properties as secondary activity, highly sought by industries. Some furan derivatives being recognized to exhibit toxicological risks, in silico and in vitro assays were conducted and demonstrated the absence of endocrine disruption activity for these new molecules.</p