Carla Villa

Eco-friendly methodologies for the synthesis of some aromatic esters, well-known cosmetic ingredients

Solid–liquid solvent‐free phase transfer catalysis (PTC) and acidic catalysis in dry media were applied, with noticeable improvement and simplification over classical procedures in a Green Chemistry context, to the synthesis of some aromatic esters useful as cosmetic ingredients: 3‐methylbutyl 4‐methoxycinnamate, 2‐ethylhexyl 4‐methoxycinnamate, 2‐ethylhexyl 4‐(dimethylamino)benzoate and 2‐ethylhexyl salicylate, well‐known ultraviolet B sunscreen filters; 4‐isopropylbenzyl salicylate, UV absorber and cutaneous antilipoperoxidant; propyl 4‐hydroxybenzoate and butyl 4‐hydroxybenzoate (parabens), antimicrobial agents. The reactions were performed under microwave (MW) activation and conventional heating. The best results for the synthesis of cinnamic, salicylic and 4‐(dimethylamino)benzoic esters were achieved by in situ preformed carboxylates alkylation with alkyl bromides using PTC. The 4‐hydroxybenzoates were obtained in good yields by classical esterification of the acid with alcohols using a simple heterogeneous mixture of reagents with catalytic amounts of p‐toluenesulfonic acid (PTSA). The comparisons of yields and thermal profiles under either MW or conventional heating were studied and reported.

Salvia somalensis essential oil as a potential cosmetic ingredient: solvent‐free microwave extraction, hydrodistillation, GC–MS analysis, odour evaluation and in vitro cytotoxicity assays

Salvia somalensis Vatke, a wild sage native of Somalia, has been studied with the aim of assessing the potential cosmetic application of its essential oil, recovered from fresh aerial parts by solvent‐free microwave extraction – SFME. To evaluate the efficiency and reliability of this ecofriendly procedure, the recovery of the essential oil was also processed by conventional hydrodistillation (HD) and the results compared. The essential oils obtained by both SFME and HD were analysed by gas chromatography–mass spectrometry using apolar and polar capillary columns. The essential oil recovered by SFME was submitted to an odour evaluation that revealed peculiar olfactive characteristics interesting in alcoholic male perfumery and body detergents.In vitro cytotoxicity assays were carried out using NCTC 2544 human keratinocytes as target cells. The oil displayed slight cytotoxic effects, which were three orders of magnitude lower than those found for sodium dodecyl sulphate positive control. The promising results in terms of chemical composition, scent and safety seem to indicate this essential oil as an interesting potential functional ingredient useful in a cosmetic context.

Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer’s disease.

Memory loss characterizes several neurodegenerative disorders, including Alzheimer’s disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising therapeutic approach to treat cognitive deficits. However, PDE4 exists in several isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here, we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both in vitro and in vivo using biochemical, electrophysiological and behavioural analyses. GEBR-32a efficiently enhances cAMP in neuronal cultures and hippocampal slices. In vivo pharmacokinetic analysis shows that GEBR-32a is rapidly distributed within the central nervous system with a very favourable brain/blood ratio. Specific behavioural tests (object location and Y-maze continuous alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance memory in AD transgenic mice and concomitantly rescues their hippocampal long-term potentiation deficit. Of great relevance, our preliminary toxicological analysis indicates that GEBR-32a is not cytotoxic and genotoxic, and does not seem to possess emetic-like side effects. In conclusion, GEBR-32a could represent a very promising cognitive-enhancing drug with a great potential for the treatment of Alzheimer’s disease.

Green Synthesis, Molecular Characterization and Associative Behavior of Some Gemini Surfactants without a Spacer Group

A series of new gemini surfactants without a spacer group, disodium 2,3-dialkyl-1,2,3,4-butanetetracarboxylates, were synthesized in a green chemistry context minimizing the use of organic solvents and applying microwaves (MW) when activation energy was required. Once the desired architecture was confirmed by means of the nuclear magnetic resonance technique (1H-NMR, 1H-1H COSY) for all the studied surfactants, the critical micellization concentration was determined by conductance measurements. The diffusion coefficient of micelles formed by the four compounds was characterized using pulsed field gradient (PFG)-NMR. Diffusion coefficients were found to be dependent on the concentration and on the number of carbon atoms in the alkyl chain. The absence of the spacer group, peculiar to this new series of gemini surfactants, may confer relatively low flexibility to the molecules, with potential implications on the interfacial properties, namely on micellization. These gemini surfactants might have interesting applications in the preparation of composite materials, in nanotechnology, in gene transfection and mainly, due to the low CMCs, as new interesting ingredients of cosmetics and toiletries.

Synthesis, biological activities and pharmacokinetic properties of new fluorinated derivatives of selective PDE4D inhibitors.

A new series of selective PDE4D inhibitors has been designed and synthesized by replacing 3-methoxy group with 3-difluoromethoxy isoster moiety in our previously reported cathecolic structures. All compounds showed a good PDE4D3 inhibitory activity, most of them being inactive toward other PDE4 isoforms (PDE4A4, PDE4B2 and PDE4C2). Compound 3b, chosen among the synthesized compounds as the most promising in terms of inhibitory activity, selectivity and safety, showed an improved pharmacokinetic profile compared to its non fluorinated analogue. Spontaneous locomotor activity, assessed in an open field apparatus, showed that, differently from rolipram and diazepam, selective PDE4D inhibitors, such as compounds 3b, 5b and 7b, did not affect locomotion, whereas compound 1b showed a tendency to reduce the distance traveled and to prolong the immobility period, possibly due to a poor selectivity.

3,3,5-Trimethylcyclohexanols and derived esters: green synthetic procedures, odour evaluation and in vitro skin cytotoxicity assays.

The alcohols 3,3,5‐trimethylcyclohexanols (cis, trans epimers, cosmetic fragrance) and some derived esters, potential and well‐known actives in the cosmetic field, such as Homosalate, were synthesized using fast solvent‐free methodologies with the aim of renewing and simplifying the conventional procedures. The alcohols were prepared by reduction of 3,3,5‐trimethylcyclohexanone (dihydroisophorone) with sodium borohydride/alumina in solid state. The esters from propanoic, butanoic, octanoic, 10‐undecenoic, cyclopropanecarboxylic, mandelic and salicylic acids were synthesized with microwave‐mediated solvent‐free procedures under acidic and basic catalysis. Several experiments were carried out to study advantages and limits of the selected methodologies and the results are reported. Microwave irradiation was carried out using a scientific monomode reactor. In order to evaluate the cosmetic interest of the studied compounds, the sweet‐scented substances were submitted to an odour evaluation test; the most promising fragrances and the ester from 10‐undecenoic acid, as an example of lipophilic derivatives, were tested to assess their in vitro skin toxicity.

Derivatization procedure and HPLC determination of 2-ethoxyethanol in cosmetic samples.

Ethylene glycol monoethyl ether or 2‐ethoxyethanol finds a wide industrial application as a solvent for lacquers, inks, dyes, household products and as a surfactant. It is also found in cosmetics such as nail products, face cleansers, liquid soaps, oral care products, hair colours and fixatives. The potential hazard to human health of 2‐ethoxyethanol following inhalation and dermal exposure has been recently reviewed and the European Cosmetic, Toiletry and Perfumery Association (COLIPA) has issued recommendations suggesting its non‐use as a cosmetic ingredient. Therefore a simple and fast monitoring method is necessary for routine control to identify and quantify 2‐ethoxyethanol in raw materials and finished cosmetics. We have developed a sensitive and selective method to determine 2‐ethoxyethanol in complex matrices by precolumn derivatization with 1‐naphthyl isocyanate and RP‐HPLC analysis. Four laboratory‐made cosmetic formulations (a nail lacquer remover, a baby oil, a skin lotion and an emollient O/W emulsion) containing three known amounts of 2‐ethoxyethanol (0.1%, 2.0%, 5.0%) have been studied. The obtained results show that this chromatographic procedure provides a good estimate of the true concentration of 2‐ethoxyethanol in complex matrices and it is reliable for routine analyses in quality control.

Green Extraction from Pomegranate Marcs for the Production of Functional Foods and Cosmetics.

The aim of this study was to investigate the potential of retrieving polyphenolic antioxidants directly from wet pomegranate marcs: the fresh by-products obtained after pomegranate juice processing. These by-products mainly consist of internal membranes (endocarp) and aril residues. Even if they are still edible, they are usually discharged during juice production and, thus, they represent a great challenge in an eco-sustainable industrial context. Green technologies, such as ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), have been employed to convert these organic residues into recycled products with high added value. UAE and MAE were used both in parallel and in series in order to make a comparison and to ensure exhaustive extractions, respectively. Water, as an environmentally friendly extraction solvent, has been employed. The results were compared with those ones coming from a conventional extraction. The most promising extract, in terms of total polyphenol yield and radical scavenging activity, has been tested both as a potential natural additive and as a functional ingredient after its incorporation in a real food model and in a real cosmetic matrix, respectively. This study represents a proposal to the agro-alimentary sector given the general need of environmental “responsible care”.

Green procedure for the preparation of scented alcohols from carbonyl compounds

Several alcohols – interesting as cosmetic fragrances whose main preparative route on an industrial scale or in the research laboratory is the reduction of the corresponding carbonyl compound – were obtained by a solvent‐free methodology in a green chemistry context. The process involves the simple mixing of the carbonyl compound with sodium borohydride dispersed in wet alumina in the solid state; the conversions of the carbonyl compounds were obtained in good yields within short reaction times, without energy consumption. The following carbinols were studied: octan‐3‐ol, 2‐cineolylols (endo–exo mixture), α‐ionol, 4‐methylbenzyl alcohol, 1‐phenylethanol, trans‐cinnamyl alcohol, p‐anisyl alcohol, 4‐phenyl‐3‐buten‐2‐ol.

Microwave-assisted Melt Reaction Method for the Intercalation of Carboxylic Acid Anions into Layered Double Hydroxides

Abstract Carboxylic acid anions intercalated layered double hydroxides are currently gaining increasing interest due to their potential applications in pharmaceutical field for controlled drug release in novel tunable drug delivery systems. In this work different aliphatic carboxylic acid anions were intercalated into the interlayers of commercial as well as synthetically prepared layered double hydroxides, through a novel microwave mediated melt reaction approach. The volumetric nature of microwave dielectric heating was exploited in order to rapidly heat the intimate mixture of the lamellar inorganic precursor and the appropriate organic acid, at the melting temperature of the particular mono-or dicarboxylic acid used, reaching the intercalation in approximately two hours treatment.