K2CO3-Promoted oxy-Michael Addition/Cyclization of α,ß-Unsaturated Carbonyl Compounds with Naphthols: Synthesis of Naphthopyrans.

A potassium carbonate promoted tandem oxy-Michael addition/cyclization of α,ß-unsaturated carbonyl compounds with naphthol derivatives for the synthesis of 2-substituted naphthopyrans was developed. Using the readily available, inexpensive potassium carbonate as the promoter, a range of different substituted naphthopyrans were prepared.

Microwave assisted synthesis of naphthopyrans catalysed by silica supported fluoroboric acid as a new class of non purine xanthine oxidase inhibitors.

A series of naphthopyrans was synthesized employing silica supported fluoroboric acid under solvent free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesised compounds were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have also been presented. Among the synthesised compounds, NP-17, NP-19, NP-20, NP-23, NP-24, NP-25 and NP-26 were the active inhibitors with an IC50 ranging from 4 to 17 µM. Compound NP-19 with a thiophenyl ring at position 1 emerged as the most potent xanthine oxidase inhibitor (IC50=4 µM) in comparison to allopurinol (IC50=11.10 µM) and febuxostat (IC50=0.025 µM). The basis of significant inhibition of xanthine oxidase by NP-19 was rationalized by its molecular docking at MTE binding site of xanthine oxidase.

Synthesis of novel photochromic pyrans via palladium-mediated reactions.

Photochromic pyrans for applications in material and life sciences were synthesized via palladium-mediated cyanation, carbonylation and Sonogashira cross-coupling starting from bromo-substituted naphthopyran 1 and benzopyrans 2a/b. A novel photoswitchable benzopyran-based omega-amino acid 6 for Fmoc-based solid-phase peptide synthesis is presented. The photochromic behaviour of the 3-cyano-substituted benzopyran 5a was investigated by time-resolved absorption spectroscopy in the picosecond time domain.

New naphthopyran analogues of LY290181 as potential tumor vascular-disrupting agents.

A series of 19 analogues of the antiproliferative naphthopyran LY290181 were prepared for structure-activity relationship studies. We found the best activities for test compounds bearing small substituents at the meta position of the phenyl ring. The mode of action of LY290181 and eight new analogues was studied in detail. The compounds were highly anti-proliferative with IC50 values in the sub-nanomolar to triple-digit nanomolar range. The new analogues led to G2/M arrest due to interruption of the microtubule dynamics. In 518A2 melanoma cells they caused a mitotic catastrophe which eventually led to apoptosis. The naphthopyrans also induced a disruption of the vasculature in the chorioallantoic membrane (CAM) of fertilized chicken eggs as well as in xenograft tumors in mice. In a preliminary therapy trial, the difluoro derivative 2b retarded the growth of resistant xenograft tumors in mice.

Naphthopyran-Based Silica Nanoparticles as New High-Performance Photoresponsive Materials.

Hybrid nanomaterials based on the covalent grafting of silylated naphthopyrans (NPTs) onto silica nanoparticles (SiO2 NPs) were successfully prepared and studied as new photochromic materials. They were prepared by a two-step protocol consisting of (i) NPTs (derivatives from 2H-naphtho[1,2-b]pyran (2H-NPT) and 3H-naphtho[2,1-b]pyran (3H-NPT)) silylation by a microwave-assisted reaction between hydroxyl-substituted NPTs and 3-(triethoxysilyl)propyl isocyanate, followed by (ii) covalent post-grafting onto SiO2 NPs. In order to study the role of the silylation step, the analogous non-silylated nanomaterials were also prepared by direct adsorption of NPTs. The characterization techniques confirmed the successful NPTs silylation and subsequent grafting to SiO2 NPs. All SiO2-based nanomaterials revealed photoswitching behavior, following a biexponential decay. The SiO2 NPs functionalized with silylated 3H-NPTs (SiO2@S3 and SiO2@S4) presented the most promising photochromic properties, showing fast coloration/decoloration kinetics (coloring in 1 min under UV irradiation and fading in only 2 min) and high values of total color difference (ΔE*ab = 30-50). Also, the 2H-NPTs-based SiO2 NPs (SiO2@S1 and SiO2@S2) presented fast coloration and good color contrasts (ΔE*ab = 54), but slower fading kinetic rates, taking more than 2 h to return to their initial color. In contrast, the SiO2 NPs functionalized with non-silylated NPTs (SiO2@1 and SiO2@3) showed weaker color contrasts (ΔE*ab = 6-10) and slower fading kinetics, proving that the NPT silylation step was crucial to enhance the photochromic behavior of SiO2 NPs based on NPTs. Furthermore, the silylated-based nanomaterials showed good photostability upon prolonged UV light exposure, keeping their photochromic performance unchanged for at least 12 successive UV/dark cycles, anticipating interesting technological applications in several areas.

Screen-Printed Photochromic Textiles through New Inks Based on SiO2@naphthopyran Nanoparticles.

Photochromic silica nanoparticles (SiO2@NPT), fabricated through the covalent immobilization of silylated naphthopyrans (NPTs) based on 2H-naphtho[1,2-b]pyran (S1, S2) and 3H-naphtho[2,1-b]pyran (S3, S4) or through the direct adsorption of the parent naphthopyrans (1, 3) onto silica nanoparticles (SiO2 NPs), were successfully incorporated onto cotton fabrics by a screen-printing process. Two aqueous acrylic- (AC-) and polyurethane- (PU-) based inks were used as dispersing media. All textiles exhibited reversible photochromism under UV and solar irradiation, developing fast responses and intense coloration. The fabrics coated with SiO2@S1 and SiO2@S2 showed rapid color changes and high contrasts (ΔE*ab = 39-52), despite presenting slower bleaching kinetics (2-3 h to fade to the original color), whereas the textiles coated with SiO2@S3 and SiO2@S4 exhibited excellent engagement between coloration and decoloration rates (coloration and fading times of 1 and 2 min, respectively; ΔE*ab = 27-53). The PU-based fabrics showed excellent results during the washing fastness tests, whereas the AC-based textiles evidenced good results only when a protective transfer film was applied over the printed design.

Synthesis and Characterization of Co-polymers Based on Methyl Methacrylate and 2-Hexyl Acrylate Containing Naphthopyrans for a Light-Sensitive Contact Lens.

Three different naphthopyrans were incorporated in co-polymers of methyl methacrylate (MMA) and 2-ethylhexyl acrylate (EHA), with and without cross-linking with ethyleneglycol dimethacrylate (EGDMA), by a free radical polymerization method. The obtained materials were characterised in terms of some of their chemical and physical properties that could be important for the final functional properties of the envisaged application. Despite other important functional properties that should be evaluated in the near future, the system based in the physical entrapment of 3,3-bis(4-methoxyphenyl)-3H-naphtho [2,1-b]pyran presented a good potential for its application as novel light-sensitive contact lenses.