Synthesis of 8-Aryl-O-methylcyanidins and Their Usage for Dye-Sensitized Solar Cell Devices

Anthocyanins as natural pigments are colorful and environmentally compatible dyes for dye-sensitized solar cells (DSSCs). To increase the efficiency, we designed and synthesized unnatural O-methylflavonols and O-methylcyanidins that possess an aryl group at the 8-position. We synthesized per-O-methylquercetin from quercetin, then using selective demethylation prepared various O-methylquercetins. Using the Suzuki-Miyaura coupling reaction, 8-arylation of per-O-methylquercetin was achieved. Using a LiAlH4 reduction or Clemmensen reduction, these flavonols were transformed to the corresponding cyanidin derivatives in satisfactory yields. Using these dyes, we fabricated DSSCs, and their efficiency was investigated. The efficiency of tetra-O-methylflavonol was 0.31%. However, the introduction of the 8-aryl residue increased the efficiency to 1.04%. In comparison to these flavonols, O-methylcyanidins exhibited a lower efficiency of 0.05% to 0.52%. The introduction of the 8-aryl group into the cyanidin derivatives did not result in a remarkable increase in the efficiency. These phenomena may be due to the poor fit of the HOMO-LUMO level of the dyes to the TiO2 conduction band.


Introduction
Anthocyanins are natural pigments that are widespread in higher plants, and the current number of isolated pigments are approaching one thousand [1][2][3][4][5]. The distinct characteristics of anthocyanins include their beautiful colors, with a wide variety of colors ranging from red to purple and blue in nature [1,5,6]. In addition, the color changes based on the pH of the media and the existence of co-pigments and/or metal ions [1][2][3][4][5][6]. Due to these properties, anthocyanins have been used as safe food colorants for a long time [7,8]. Recently, anthocyanins have attracted increasing attention as functional colorants for lifestyle-related diseases [9][10][11] and potential dyes for dye-sensitized solar cells (DSSCs) devices [12,13], which are next-generation solar cells with low production costs and flexibility. To expand these studies, development of an efficient synthetic procedure of dyes is essential.
To synthesize anthocyanins, the metal reduction of flavonols to their corresponding anthocyanidins (anthocyanins) has been previously reported in the early 20th century [14][15][16]. This synthetic route is very effective because the transformation is achieved in a single-step reaction without any protecting groups at the polyphenolic hydroxyl groups. A long time after those reports, Brouillard and his group reported the reduction of flavonols using Zn-Hg in 1995 [17]; however, the yield was not satisfactory. We re-investigated this reaction procedure and improved the reaction conditions using Zn powder rather than Zn amalgam and reported that anthocyanins can be obtained in a yield of more than 80% [18]. Using this method, several anthocyanins including acylated anthocyanins can be obtained from the corresponding flavonols [18,19]. This method was expanded to synthesize unnatural anthocyanidins. For this purpose, we first synthesized various methylated quercetins [20] and 8-substituted quercetins [21]. After selective demethylation, the reduction of these flavonols afforded substituted cyanidins in good yields.
DSSCs studies using anthocyanins have been carried out by several groups [22][23][24][25][26] because anthocyanin contains no metal ions and is environmentally friendly. However, the efficiency η% value of the DSSCs using pure anthocyanins and/or extracts from plants was low (i.e., approximately 1.0%) [22][23][24][25]. In 2013, Calogero et al. reported an efficiency of 2.2% using synthetic anthocyanidin [27]. We fabricated DSSCs using five pure natural anthocyanidin 3-O-glucosides with different chromophores and compared the color of the cells as well as their efficiencies [28]. These pigments resulted in beautiful cells that were blue due to petunidin 3-O-glucoside and purplish blue due to delphinidin 3-O-glucoside. However, the efficiency was still not high (i.e., approximately 1% to 1.4%) [28]. The time-dependent density functional theory (TD-DFT) calculations for the anthocyanidin dye model cluster systems (dye/(TiO 2 ) 38 ) revealed that both indirect (Type-I) and direct (Type-II) electron injection mechanisms may co-exist [28]. In addition, the highest occupied molecular orbital (HOMO)-the lowest unoccupied molecular orbital (LUMO) level of the dye may not match well with the conduction band of TiO 2 , which may result in low efficiency of the anthocyanin dye-based DSSCs. A preliminary calculation indicated that introduction of an aryl group at the 8-position may increase the HOMO level of the dye to match the conduction band of TiO 2 . Therefore, we designed 8-arylanthocyanidin for use as a DSSC dye. We synthesized O-methylquercetins and 8-aryl-O-methylquercetins from quercetin. The number of methyl moieties was varied by selective demethylation [20]. These methylquercetin derivatives were transformed to the corresponding O-methylcyanidins and 8-aryl-O-methylcyanidins via reduction. Using the synthesized derivatives, we fabricated DSSCs, and the photoelectric conversion efficiency was measured.

Synthesis of O-Methylquercetins
The synthetic strategy for various O-methylquercetins and O-methylcyanidins bearing an 8-aryl group is shown in Scheme 1. First, we prepare per-O-methylquercetin (2) via permethylation of quercetin (1), and then, various O-methylquercetins with different numbers of methyl moieties were prepared via regioselective demethylation. In addition, regioselective iodination afforded 8-iodo per-O-methylquercetin (3), and then, Suzuki-Miyaura coupling afforded 8-aryl-O-methylquercetins. The quercetin derivatives were reduced to yield the corresponding O-methylcyanidins. Using this scheme, quercetin and cyanidin derivatives with different numbers of O-methyl residues and varied 8-aryl groups were prepared.

Synthesis of O-Methylanthocyanidins
The as-prepared O-methylquercetins were transformed to cyanidin derivatives (Scheme 1). Our preliminary experiments suggested that Clemmensen-type reduction of 3,5,7,3 4 -penta-O-methylquercetin (2) using Zn/HCl [18] resulted in a messy product, and the yield of 3,5,7,3 4 -penta-O-methylcyanidin (17) was low. The well-known transformation from penta-O-methylquercetin (2) to 3,5,7,3 ,4 -penta-O-methylcyanidin (17) using a combination of LiAlH 4 and an oxidant was first reported in 1968 [34,35]. At that time, a large amount of LiAlH 4 was used, and after the reduction, re-oxidation was carried out to afford anthocyanidins. We re-investigated the transformation reaction and found that the reduction of 2 with 4 eq. of LiAlH 4 at room temperature afforded 17 in 70% yield without any oxidant [21]. In addition, quercetin derivatives possessing a 5-OH structure were transformed to the corresponding cyanidin compounds via a Clemmensen-type reduction [18]. Therefore, in this study, we employed both reaction conditions depending on the structure of the substrate.

Photovoltaic Property of DSSCs Using O-Methylquercetins
First, we fabricated DSSCs with five O-methylquercetins (2, 4-7) where the number of methylations differed. Their photovoltaic properties with AM 1.5 irradiation are shown in Table 4. N719 was used as the standard dye. Although 4-tert-butylpyridine (TBP) was typically added to the electrolyte to increase Voc [36,37], preliminary experiments indicated that TBP (0.5 mM) did not provide good results. Therefore, we performed the experiment without TBP. The cells with penta-Omethylquercetin (2), tetra-O-methylquercetin (4) and tri-O-methylquercetins (5) possessed a pale yellow color, and the cells with di-O-methylquercetin (6) and mono-O-methylquercetins (7) were orange, indicating that these dyes may be adsorbed to TiO2 with the dihydroxyl group of the B-ring. The efficiencies (η%) of the DSSCs of O-methylquercetins were not high (i.e., ranging from 0.09%-0.82%). Quercetin (1) and mono-O-methylquercetin (7) exhibited a similar efficiency (ca. 0.6%), and the highest (i.e., 0.82%) efficiency was observed for di-O-methylquercetin (6). We proposed that methylation may increase the hydrophobicity of the compounds, which would result in an increase

Photovoltaic Property of DSSCs Using O-Methylquercetins
First, we fabricated DSSCs with five O-methylquercetins (2, 4-7) where the number of methylations differed. Their photovoltaic properties with AM 1.5 irradiation are shown in Table 4. N719 was used as the standard dye. Although 4-tert-butylpyridine (TBP) was typically added to the electrolyte to increase V oc [36,37], preliminary experiments indicated that TBP (0.5 mM) did not provide good results. Therefore, we performed the experiment without TBP. The cells with penta-O-methylquercetin (2), tetra-O-methylquercetin (4) and tri-O-methylquercetins (5) possessed a pale yellow color, and the cells with di-O-methylquercetin (6) and mono-O-methylquercetins (7) were orange, indicating that these dyes may be adsorbed to TiO 2 with the dihydroxyl group of the B-ring. The efficiencies (η%) of the DSSCs of O-methylquercetins were not high (i.e., ranging from 0.09%-0.82%). Quercetin (1) and mono-O-methylquercetin (7) exhibited a similar efficiency (ca. 0.6%), and the highest (i.e., 0.82%) efficiency was observed for di-O-methylquercetin (6). We proposed that methylation may increase the hydrophobicity of the compounds, which would result in an increase of the efficiency. However, this behavior was not observed. The incident photon-to-current conversion efficiency (IPCE) spectra indicated that these compounds only absorbed light energy shorter than 500 nm, and a peak was observed at approximately 400 nm at a maximum of 60% with di-O-methylquercetin (6). Table 4. Photovoltaic properties of the dye-sensitized solar cells (DSSCs) sensitized with O-methyl quercetins (1, 2, 4-7 Because O-methylquercetins are flat molecules that most likely stack on each other followed by quenching the harvested energy via intermolecular charge transfer, a hindered residue was introduced to prevent this phenomenon. In addition, an aryl group at the 8-position of the quercetin chromophore was introduced as an electron-donating residue, which may increase HOMO level. Based on results from preliminary experiments, we chose the 8-phenyl, 8-naphthyl and 8-(4-(diphenylamino)phenyl-residues for the substituents and prepared nine 8-aryl-O-methylquercetins (8)(9)(10)(11)(12)(13)(14)(15)(16) for use as DSSC dyes. The photovoltaic properties are shown in Table 5. Similar to the methylquercetins, the cell color of the penta-O-methyl derivatives and tetra-O-methyl derivatives were yellow, and the di-O-methyl compounds were orange. Among these compounds, the efficiency of 8-naphthyl-3,7,3 ,4 -tetra-O-methylquercetin (12) exhibited a high value of 1.04% (Table 5). Other 8-aryl-3,7,3 ,4 -tetra-O-methylquercetins also exhibited a higher η% compared to that of tetra-O-methylquercetin (4). The efficiencies of the 8-aryl-3,7-di-O-methylquercetins (14)(15)(16) were 0.67%-0.88%, which is nearly the same as that of 3,7-di-O-methylquercetins (6). The introduction of the 8-aryl residue to 3,5,7,3 ,4 -penta-O-methylquercetin did not result in any increase in η% and exhibited a very low efficiency of 0.03%-0.06%. For these nine compounds, the efficiency may be affected by a balance of many factors, such as the hydrophobicity, electron density, and the adsorption to TiO 2 , which may cause complicated results.

Preparation of DSSCs
We prepared the DSSCs according to the method reported by Liu et al. with slight modifications [28,38]. TiO 2 films for use as photoanodes were prepared by screen-printing TiO 2 pastes with different particle diameters (11-400 nm) onto F-doped SnO 2 glass. After treating the glass with a TiCl 4 solution, the films were calcined using the following temperature program: heat from room temperature (rt) to 200 • C for 15 min, from 200 to 500 • C for 15 min, hold at 500 • C for 30 min, and then cool to rt. The TiO 2 electrodes were immersed in methanol or acetonitrile solution and then maintained at room temperature (rt) for or 18 h. After dye loading, the films were removed and rinsed with acetonitrile. The dye-loaded TiO 2 electrodes were sandwiched between commercially available Pt counter electrodes (Geomatec Co., Ltd., Yokohama, Japan) with electrolyte filling the gap separated by a spacer (HIMILAN: DuPont-Mitsui Polychemicals Co., Ltd., Tokyo, Japan). The active area of the cells was 0.16 cm 2 . Iodide (I − /I 3 − ), which is a commonly used electrolyte, was used as the electrolyte in this study [38]. 4-tert-Butylpyridine (TBP) was occasionally added. The thicknesses of the TiO 2 films on the FTO glasses were measured after the performance evaluation using a SURFCOM 130A (ACCRETECH Co., Ltd., Tokyo, Japan). The average thickness was approximately 10 ± 1 µm.

Measurement of the Cell Properties
The measurement of the cell properties was performed according to a previously reported protocol [28,38]. The current-voltage (J-V) characteristics of the cells were measured using an AM 1.5 solar simulator (OTENTO-SUN III, Bunkoukeiki Co., Ltd., Tokyo, Japan). The data were collected by a source meter (Keithley 2400), and the light-to-electricity conversion efficiency (η) was obtained from the following equation: η = (J sc × V oc × FF)/P in , where J sc is the short-circuit photocurrent density, V oc is the open-circuit voltage, FF is the fill factor, and P in is the incident radiation power. The incident monochromatic photon-to-current conversion efficiency (IPCE) spectra were measured using an IPCE measurement system (SM-250 hyper mono light system, Bunkoukeiki Co., Ltd.). The IPCE values were obtained by comparing the current ratio and the IPCE value of the reference cell at each wavelength. The light intensity of the illumination source was adjusted using standard silicon photodiodes, i.e., BS520 for J-V characteristics and SiPD S1337-1010BQ for external quantum efficiency (EQE) measurements (Bunkoukeiki Co., Ltd.).

Conclusions
We designed and synthesized four O-methylcyanidins, as well as three types of 8-aryl-Omethylquercetins and cyanidins, including several new compounds. The introduction of the 8-aryl residue was established with a Suzuki-Miyaura coupling of 8-iodo-per-O-methylquercetin, and reduction of the quercetin derivatives to the corresponding cyanidin compounds was achieved in satisfactory yield. This synthetic route is very practical and efficient for the preparation of substituted flavonols and anthocyanidins. In the near future, the function of these compounds to prevent metabolic syndromes in humans will be studied. Using these flavonoids, we fabricated DSSCs and evaluated their photovoltaic efficiency. The efficiency was relatively low compared to that of natural flavonols and anthocyanins, which may be due to intermolecular stacking of the compounds, and the harvested energy may be quickly quenched before the electron reaches the electrode. Further molecular design and preparations are underway.