Synlett 2020; 31(04): 334-338
DOI: 10.1055/s-0039-1690744
letter
© Georg Thieme Verlag Stuttgart · New York

Bioinspired Synthesis and Physical-Chemical Properties of a New 10-Methylpyrano-4′-hydroxyflavylium Chloride Salt

Vânia Gomes
,
Marta Guimarães
,
Gabriela Gonçalves
,
Victor de Freitas
,
Luís Cruz
REQUIMTE/LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal   Email: luis.cruz@fc.up.pt
› Author Affiliations
This research was supported by a research project grant (PTDC/OCE-ETA/31250/2017) with financial support from FCT/MEC through national funds and was co-financed by FEDER under the Partnership Agreement PT2020 (UID/QUI/50006/2019-POCI/01/0145/FERDER/ 007265, 2017). L.C. acknowledges an FCT research contract and V. G. acknowledges receipt of a Ph.D. grant from FCT (SFRH/BD/136556/2018).
Further Information

Publication History

Received: 04 October 2019

Accepted after revision: 24 October 2019

Publication Date:
07 November 2019 (online)


Published as part of the Special Section 11th EuCheMS Organic Division Young Investigator Workshop

Abstract

A novel bioinspired 10-methylpyranoflavylium dye was synthesized. The dye was fully characterized by LC-DAD/ESI-MS and NMR 1D and 2D techniques, and its equilibrium constants towards pH variations were determined by UV–vis titration. These studies revealed the presence of three species (a flavylium cation AH+, a neutral quinoidal base A, and an anionic quinoidal base A) in the pH range 1–12, driven by the two pK a values of the dye: pK a1 = 6.8 ± 0.1 and pK a2 = 10.8 ± 0.1. The first deprotonation of the dye occurs within the pH range for spoilage of many packed-food products, making the dye an excellent candidate for use as a pH sensor for real-time monitoring of the quality and freshness of foods.

Supporting Information

 
  • References and Notes

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  • 13 5-Hydroxy-2-(4-hydroxyphenyl)chromenium Chloride (3) 2,6-Dihydroxybenzaldehyde (1; 204 mg, 1.48 mmol) and 4-hydroxyacetophenone (2; 1 equiv) were dissolved in 2:1 EtOAc–MeOH (5 mL), and the solution was cooled to 0 °C. TMSCl (20 equiv) was added, and the mixture was stirred for 60 min. The product was precipitated by addition of EtOAc, and the solid was collected by filtration and washed with Et2O to give a dark-orange powder; yield: 227 mg (56%). 1H NMR (600.13 MHz, 9:1 DMSO-d6 –TFA): δ = 9.29 (d, J = 9.1 Hz, 1 H, H4), 8.53 (d, J = 9.1 Hz, 1 H, H3), 8.50 (d, J = 8.8 Hz, 2 H, H2′, H6′), 8.00 (t, J = 8.3 Hz, 1 H, H7), 7.61 (d, J = 8.5 Hz, 1 H, H6 or H8), 7.20 (d, J = 8.1 Hz, 1 H, H6 or H8), 7.11 (d, J = 8.8 Hz, 2 H, H3′, H6′). 13C NMR (125.77 MHz, 9:1 DMSO-d6 –TFA): δ = 174.3 (C2), 168.2 (C4′), 157.5 (C5 or C8a), 155.9 (C5 or C8a), 150.2 (C4), 140.2 (C7), 134.6 (C2′, C6′), 119.9 (C3′, C5′), 118.3 (C1′), 115.5 (C4a), 115.1 (C3), 113.3 (C6 or C8), 108.6 (C6 or C8). LC-DAD/ESI-MS: m/z = 239 [M]+. UV–vis: λmax = 440 nm.
  • 14 2-(4-Hydroxyphenyl)-5-methylpyrano[4,3,2-de]chromen-1-ium Chloride (4) The dihydroxyflavylium chloride 3 (50 mg, 0.18 mmol) was dissolved in 10:90 acetone–H2O, and the mixture was stirred at 37 °C and pH 2.9 for 3 d. The mixture was then extracted with Et2O, and the aqueous fraction was purified by reverse-phase column chromatography [C18 silica gel, MeOH–H2O (10:90) acidified with 2% HCl]. The solvent was evaporated, and the product was freeze dried to give a dark-orange powder; yield: 17 mg (30%). 1H NMR (600.13 MHz, 9:1 DMSO-d6 –TFA): δ = 8.24 (d, J = 8.93 Hz, 2 H, H2′, H6′), 8.21 (t, J = 8.42 Hz, 1 H, H7), 7.88 (s, 1 H, H3), 7.87 or 7.73 (d, J = 4.21 Hz, 1 H, H8), 7.73 or 7.87 (d, J = 4.21 Hz, 1 H, H6), 7.09 (s, 1 H, H9), 7.06 (d, J = 8.90 Hz, 2 H, H3′, H5′), 2.65 (s, 3 H, CH3). 13C NMR (125.77 MHz, 9:1 DMSO-d6 –TFA): δ = 174.0 (C10), 170.0 (C2), 165.4 (C4′), 153.4 (C8a), 152.7 (C5), 137.4 (C7), 131.8 (C2′,C6′), 120.0 (C1′), 117.3 (C3′,C5′), 113.0 (C4a), 106.5 (C9), 102.4 (C3), 21.5 (CH3). LC-DAD/ESI-MS: m/z = 277 [M+]. UV–vis: λmax = 460 nm.
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  • 18 Cruz L, Borges E, Silva AM. S, Mateus N, de Freitas V. Lett. Org. Chem. 2008; 5: 530
  • 19 HPLC-DAD analyses were performed on a Merck-Hitachi L-7100 apparatus with a 150 × 4.6 mm i.d. reverse-phase ODS C18 column (Merck, Darmstadt) at 25 °C. Detection was carried out using a L-7450A diode array detector (DAD). The eluents were A: H2O–HCO2H (9:1) and B: CH3CN. The gradient consisted of 0–35% B for 50 min at a flow rate of 0.5 mL/min. The column was washed with 100% B over 10 min and then stabilized to the initial conditions during another 10 min.
  • 20 LC-DAD/ESI-MS: LC-DAD/ESI/MS analyses were performed on a Finnigan Surveyor series liquid chromatograph equipped with a Finnigan LCQ mass detector and an API source using an ESI interface. The samples were analyzed on a reverse-phase column (150 × 4.6 mm, 5 μm, C18) at 25 °C using the same eluents, gradients and flow rates as used for HPLC analysis (see Ref. 19). The capillary voltage was 4 V and the capillary temperature was 275 °C. Spectra were recorded in positive- and negative-ion modes between m/z = 120 and m/z = 1500. The mass spectrometer was programmed to carry out a series of three scans: a full mass scan, a zoom scan of the most intense ion in the first scan, and an MS–MS of the most intense ion using a relative collision energy of 30 and 60.
  • 21 The 1H NMR (600.13 MHz) and 13C NMR (125.77 MHz) spectra were recorded in 95:5 DMSO–TFA on a Bruker-Avance 600 spectrometer at 303 K, with TMS as an internal standard. 1H chemical shifts were assigned by using 2D NMR (COSY, NOESY) experiments, whereas 13C resonances were assigned by using 2D NMR techniques (gHMBC and gHSQC). The delay for the long-range C–H coupling constant was optimized to 7 Hz.
  • 22 UV-Vis Titration A 0.3 mM pigment stock solution was prepared in 0.1 M HCl in 75:25 EtOH–H2O. A quartz cell was charged with Teorell and Stenhagen universal buffer23 at pH 1 (1 mL), 0.1 M aq NaOH (1 mL), and the pigment stock solution (1 mL). The final concentration of the pigment was 0.1 mM in 25% EtOH. Titrations were performed up to pH 12 by the addition of small volumes of 1 M aq NaOH. Successive spectra were recorded immediately after the addition of the base in a Thermo Scientific Evolution Array UV–Visible spectrophotometer at 25 °C. All titrations were performed in triplicate. Final volumes were appropriately corrected. All pH measurements were made with a Radiometer Copenhagen PHM240 pH/ion meter. The fitting for pK a determinations was carried out by using the Solver add-in program for Microsoft Excel.
  • 23 Teorell and Stenhagen universal buffer was prepared by dissolving phosphoric acid (2.25 mL, 85% w/w), boric acid (3.54 g), monohydrated citric acid (7.00 g), and 1 M aq NaOH (343 mL) in distilled water to a volume of 1 L.
  • 24 Gomes V, Mateus N, de Freitas V, Cruz L. Dyes Pigm. 2019; 167: 60
  • 25 Pacquit A, Frisby J, Diamond D, Lau KT, Farrell A, Quilty B, Diamond D. Food Chem. 2007; 102: 466
  • 26 Zhang X, Lu S, Chen X. Sensors Actuators B: Chem. 2014; 198: 268