Development of an intramolecular charge transfer-type colorimetric and fluorescence sensor for water by fusion with a juloidine structure and complexation with boron trifluoride

An optical sensor with the ability to detect and determine water over a wide concentration range is highly desirable in the laboratory and industry. Here the sensitivity and spectral responses of an intramolecular charge transfer-type colorimetric and fluorescence sensor with β-carboline structure are tuned and improved significantly over various water contents in the organic solvent by fusion with an electron-donating juloidine structure and complexation with boron trifluoride (BF3). The sensors, ET-1 and ET-1-BF3, developed in this study can respond differently depending on water content. ET-1-BF3 releases BF3 to generate ET-1 by addition of a trace amount of water, and ET-1 forms hydrogen bonds with one water molecule in low water contents and a hydrogen-bonded proton transfer complex with several water molecules in high water contents, accompanying gradual color and fluorescence changes. This work shows a promising approach to the sensitive detection and precise determination of water over the whole concentration range using a simple and practical method with optical sensors.


Introduction
The detection and determination of water are of great importance in industrial applications, including food inspection, biomedical and environmental monitoring, and manufacturing of pharmaceutical, electronic, and petroleum products. 1 In synthetic chemistry, the presence of water in organic solvents causes serious problems, such as generation of by-products, quenching of reactions, lowering of the product yields, and furthermore, catastrophic dangers of re and explosion. Particularly, in a large-scale industrial process, careful attention is paid to this impurity to avoid worst-case scenarios. Therefore, various analytical approaches and techniques have been developed to detect and determine water content in organic solvents. The standard Karl Fischer titration is the most popular method and allows for quantitative measurements of water over a wide range of the concentrations (0.001-100% water) with high sensitivity and wide applicability for a large variety of samples; 2,3 however, it has several limitations, e.g., instability, time-consuming procedure, and use of toxic chemical reagents and costly specialized instrumentation. Therefore, in recent years, the method using optical water sensors has attracted much attention because of its considerable advantages of simple operation, low-cost fabrication, fast response, high sensitivity, non-destructive nature, and remote and in situ monitoring even by the naked eye. 4 Although most research studies on the optical sensors have been focused on the detection and determination of a trace amount of water, 5-28 sensors that can work over a wide range of water concentrations (similar to the range the Karl Fischer method can cover) are also required.
In the optical sensor method, water content can be determined by measurement and ratiometric analysis of the optical properties of small-quantity sensor molecules doped in sample solutions, i.e., wavelength, intensity, lifetime, and quantum yield of photoabsorption and photoluminescence. Therefore, the optical properties should be sensitive to water molecules and variable depending on the water content. Several strategies have been demonstrated to meet the requirement, such as intramolecular charge transfer (ICT), 5-9 excited state intramolecular proton transfer (ESIPT), [9][10][11] photo-induced electron transfer (PET), 12-18 aggregation-induced emission (AIE), 7,29,30 decoloration of hydrogen-bonding photochromic dyes, 31 and other water-triggered mechanisms. [19][20][21][22][23][24][25][26][27][28] Generally, in each system, there is a specic range of water concentration available for detection; AIE is observed in high water concentrations, 7,29,30 whereas other systems exhibit optical changes in a relatively low concentration range.  In this context, a reasonable approach to incorporating two mechanisms into one sensor molecule has been developed to detect and determine water in organic solvent sensitively in a wide concentration range, including the combinations of ICT or PET and AIE, 32-39 two water-induced reactions, 40 and two ICT-related mechanisms, 41,42 with rare exceptions based on one mechanism. 23,[43][44][45][46][47][48][49] However, the pioneering systems still have several problems to be solved, such as the appearance of non-response ranges to variations in water content and the indiscernible small changes in the photoabsorption and uorescence spectra as well as by the naked eye.
Herein, we report the tuning of sensitivity of optical sensors to water molecules and improvement in the spectral variations over a wide range of water content in an organic solvent. We focused on the b-carboline-based water sensor, 9-MP, 50 with a small electron donor-acceptor (D-A) structure and its complex with boron triuoride (BF 3 ), 9-MP-BF 3 , 42 as shown in Fig. 1, because they exhibit a unique multi-step response to increasing water content in organic solvent, i.e., release of BF 3 (only in 9-MP-BF 3 ), hydrogen bonding with one water molecule, and formation of hydrogen-bonded proton transfer complex (PTC) [50][51][52][53][54][55][56][57][58] with several water molecules, accompanying gradual spectral changes in photoabsorption and uorescence based on the D-A structure and ICT. However, these systems also lack the capability to detect and determine water in moderate concentrations (ca. 10-40 wt%) and show the indiscernible optical changes particularly in photoabsorption spectra also in the other ranges. 42,50 Since the unique response is owing to the moderate basicity of the pyridinic nitrogen atom in the b-carboline skeleton, in this study, we modulated the basicity and enhanced the D-A and ICT characteristics by fusion of the bcarboline skeleton with a strong electron donor, juloidine, 59 developing new water sensors, ET-1 and ET-1-BF 3 . Their watersensing ability and sensing mechanisms were investigated in acetonitrile with various water contents, and the strategy for tuning of the sensitivity to water and improvement in spectral response over a wide range of water content were demonstrated.

General methods
Melting points were measured using a Yanaco micro melting point apparatus MP model. IR spectra were recorded on a Shimadzu IRAffinity-1 spectrometer using the ATR method. Highresolution mass spectral data were acquired using a Thermo Fisher Scientic LTQ Orbitrap XL. 1 H NMR, 13 C NMR, and 11 B NMR spectra were recorded using Varian-400 (400 MHz) and Varian-500 (500 MHz) FT NMR spectrometers. Photoabsorption spectra were recorded using a Shimadzu UV-3150 spectrophotometer and uorescence spectra were recorded using a HITA-CHI f-4500 uorescence spectrometer. The determination of water in acetonitrile solution was done with MKC-610 and MKA-610 Karl Fischer moisture titrators (Kyoto Electronics manufacturing Co., Ltd.) based on Karl Fischer coulometric titration (relative standard deviation is below 0.3% in a measurement of methanol containing 1 mg water) for below 1.0 wt% and volumetric titration for above 1.0 wt%, respectively.

Results and discussion
The juloidine-conjugated b-carboline complexed with BF 3 , ET-1-BF 3 , was effectively prepared by treating the corresponding bcarboline derivative, ET-1, with BF 3 -OEt 2 and characterized by 1 H NMR, 13 C NMR, 11 B NMR, and FT-IR measurements and high-resolution mass analysis.
The photoabsorption and uorescence spectra of ET-1 and ET-1-BF 3 in acetonitrile are shown in Fig. 2. The photoabsorption maxima (l abs max ) of ET-1 and ET-1-BF 3 were observed at 365 and 436 nm, respectively, which originate from the ICT  excitation from the electron-donating julolidine moiety to the electron-withdrawing pyridine moiety in ET-1 or to its complex with BF 3 in ET-1-BF 3 . Because the strong electron-withdrawing ability of the pyridine complex with BF 3 enhances the ICT characteristic, the photoabsorption maximum of ET-1-BF 3 was observed at longer wavelength region by 71 nm than that of ET-1. Additionally, the molar excitation coefficient value (3) of ET-1-BF 3 (25 900 M À1 cm À1 ) was higher than that of ET-1 (19 900 M À1 cm À1 ). Similarly, the corresponding uorescence bands of ET-1 and ET-1-BF 3 appeared at 411 and 507 nm (l  max ), respectively, and the uorescence quantum yields (F f ) were 0.38 (ET-1) and 0.65 (ET-1-BF 3 ). These results indicate that the complexation of ET-1 with BF 3 caused not only the bathochromic shis of the photoabsorption and uorescence bands but also the increases in 3 and F f values. Furthermore, compared with 9-MP and 9-MP-BF 3 in acetonitrile, 42,59 the fusion with juloidine could improve their photophysical properties (l abs max ¼ 358 and 388 nm, 3 ¼ 5800 and 3300 M À1 cm À1 , l  max ¼ 368 and 458 nm, and F f ¼ 0.04 and 0.52 for 9-MP and 9-MP-BF 3 , respectively). In order to investigate the ability of ET-1 and ET-1-BF 3 as optical sensors for water in organic solvent, the photoabsorption and uorescence measurements were performed in acetonitrile with various water contents ( Fig. 3 and 4). In the case of ET-1, the photoabsorption band at around 360 nm slightly increased in intensity and bathochromically shied with increase in water content up to 11 wt%, and two isosbestic points were observed at 298 and 354 nm (Fig. 3b). These small spectral changes can be ascribed to the formation of the hydrogen-bonded complex (ET-1-H 2 O) between the pyridinic nitrogen atom and one water molecule. 42,50-58 Above 11 wt%, the photoabsorption band decreased in intensity and red-shied distinctly, while a new photoabsorption band appeared simultaneously at around 430 nm (Fig. 3c). The new band is assignable to the ICT band of the hydrogen-bonded PTC (ET-1-H + ) formed by the proton transfer from water molecule to the pyridinic nitrogen atom. Since the photoabsorption spectra of 9-MP changed negligibly over the whole range of water content, 42,50 these results indicate that the fusion of juloidine and the enhanced ICT characteristic improved its spectral responses to water. Similar behavior was also observed in the uorescence spectra of ET-1. The solution showed a small red-shi and increase in intensity of the uorescence band at around 420 nm by addition of water up to 11 wt% (Fig. 3e), indicating the formation of the hydrogen-bonded complex (ET-1-H 2 O). From 11 wt%, the intensity of the uorescence band started decreasing signicantly, while a new band originating from the hydrogen-bonded PTC (ET-1-H + ) simultaneously appeared at around 510 nm and increased in intensity with an isoemissive point at 475 nm (Fig. 3f). In the previous study, 59 these spectral changes were observed by not increasing the static dielectric constant of solvent but changing the solvent to hydrogen-bonding protic one. From these results, we concluded that the hydrogen-bonded complex (ET-1-H 2 O) started forming from a trace content of water, followed by the simultaneous generation of the hydrogen-bonded PTC (ET-1-H + ) above 11 wt%. Additionally, it is noteworthy that ET-1 started forming the hydrogen-bonded PTC from the lower water content (11 wt%) compared to 9-MP (from 40 wt%) 42,50 due to the enhanced basicity of the pyridinic nitrogen atom in ET-1 and resulting promotion of the PTC formation, indicating a successful tuning of the sensitivity over a wide range of water content.
In the case of ET-1-BF 3 , the photoabsorption and uorescence spectral responses to water were complicated. First, we examined the time dependence of the spectra aer addition of a tiny amount of water. In the photoabsorption and uorescence spectra, large differences were observed between the ET-1-BF 3 acetonitrile solutions that were stored in the dark for 10 min or 1 day aer addition of 0.0201 wt% of water ( Fig. 4a  and d). The longer storage time caused signicant decreases in intensity of the photoabsorption band at around 430 nm and uorescence band at around 510 nm and also increases in intensity of the photoabsorption band at around 360 nm and uorescence band at around 420 nm. Because the timedependent spectral changes are attributed to the waterinduced release of BF 3 and generation of ET-1, 41,42 the results indicate that the reaction occurs with a trace amount of water but takes a relatively long time. Therefore, we employed the solutions stored in the dark for 1 day aer adding various amounts of water for the following photoabsorption and uorescence measurements. By the addition of water up to 11 wt%, the photoabsorption band at around 430 nm drastically decreased in intensity and almost disappeared with simultaneous increase of that at around 360 nm, which originates from ET-1 generated as a result of the BF 3 release (Fig. 4b). From 11 wt%, the photoabsorption band at around 360 nm decreased in intensity, while that at around 430 nm reappeared and increased, indicating the formation of the hydrogen-bonded PTC (ET-1-H + ) (Fig. 4c). The formation of the hydrogenbonded complex (ET-1-H 2 O) is seen from the bathochromic shi of the photoabsorption band at around 360 nm in a wide range above 2.3 wt% (below 40 wt%) (Fig. 4b and c). In the spectra, isosbestic points were observed at 272 and 293 nm below 2.3 wt% and 272, 305, and 386 nm above 40 wt% of water content. In the corresponding uorescence spectra (Fig. 4d-f), the intensity of the band at around 510 nm originating from ET-1-BF 3 decreased with increase of that at around 420 nm originating from ET-1 below 11 wt% of water content (Fig. 4e). In the range, the band at around 420 nm red-shied with increase in water content, indicating the simultaneous formation of ET-1-H 2 O. 42,50-58 Above 11 wt%, the uorescence band at around 420 nm decreased in intensity, while that at around 510 nm signicantly increased with an isoemissive point at 475 nm, due to the generation of ET-1-H + (Fig. 4f). From the comparison between Fig. 3 and 4, it can be concluded that the sensitivity and spectral response to water could be further improved in the low water contents by the complexation of the juloidine-conjugated b-carboline sensor (ET-1) with BF 3 . To evaluate the optical sensing ability in detail, the peak intensities of photoabsorption and uorescence bands were plotted against the water content in acetonitrile solutions of ET-1 (Fig. 5) and ET-1-BF 3 (Fig. 6). In the case of ET-1, although the maximum intensities of the photoabsorption bands at around 360 (A 360 ) and 430 (A 430 ) nm were almost unchanged upon increase in water content below 11 wt% (Fig. 5b), A 360 decreased and A 430 increased linearly as a function of water content in the range of 11-60 wt% (Fig. 5c). The slopes (m s ) in the plots and the correlation coefficient values (R 2 ) for the calibration curves are À0.001 and 0.97 for A 360 and 0.002 and 0.91 for A 430 , respectively. On the other hand, the maximum intensities of the uorescence bands at around 420 (FL 420 ) and 510 (FL 510 ) nm increased with increase in the water content even below 11 wt% due to the formation of ET-1-H 2 O (Fig. 5e). The m s and R 2 values for FL 510 are 2.3 and 0.99, respectively, which show good response and linearity. Moreover, the plots of FL 420 and FL 510 show signicant decrease and increase, respectively, with increasing water content above 11 wt% due to the generation of ET-1-H + (Fig. 5f). The linear relationships were also observed between the uorescence intensities (FL 420 and FL 510 ) and water content in the 11-40 wt% range. The m s and R 2 values are À16 and 0.95 for FL 420 and 9.0 and 0.95 for FL 510 , respectively. These results, i.e., the linear relationships observed over the wide range of water content, suggest that the precise determination of water in organic solvent is possible over a wide range by using a small amount of ET-1 as an optical sensor.
ET-1-BF 3 showed distinctly different behavior from ET-1 below 11 wt% of water content (Fig. 6). The photoabsorption and uorescence intensities drastically changed with increasing water content, although thresholds were observed at around 1 wt% (Fig. 6b and f). The slow release of BF 3 and incomplete conversion within the reaction time (1 day) would cause the appearance of the thresholds. Indeed, the thresholds disappeared in the plots obtained using the solutions stored in the dark for 2 days (Fig. S1, ESI †). In the water content range of 1.1-4.2 wt%, A 360 increased but A 430 decreased in a linear fashion with increase of water content (Fig. 6b). The m s and R 2 values are 0.05 and 0.99 for A 360 and À0.09 and 0.99 for A 430 , respectively. Similar contrasting behavior were observed between the plots of FL 420 and FL 510 in the low content range with linear relationships (Fig. 6f). The large m s values (68 for FL 420 and À28 for FL 510 ) and the R 2 values close to 1 (0.99 for FL 420 and FL 510 ) indicate a superior performance (sensitivity and accuracy) of ET-1-BF 3 as a water sensor, although the presence of thresholds precludes estimation of the detection limits. In the 4.2-11 wt% range, only slight changes were observed in the photoabsorption and uorescent intensities ( Fig. 6c and g). However, in the higher water content range of 11-60 wt%, A 360 and A 430 distinctly changed (m s ¼ À0.002 and 0.002, respectively) with linear relationships (R 2 ¼ 0.96 and 0.98, respectively) due to the formation of ET-1-H + (Fig. 6d), as is the case for ET-1 (Fig. 5c). Moreover, FL 420 decreased and FL 510 increased linearly as a function of the water content in the 11-40 wt% range (m s ¼ À0.002 and 0.002 and R 2 ¼ 0.95 and 0.96, respectively) (Fig. 6h). These values show good agreement with those observed in the ET-1 solutions (Fig. 5f). Therefore, the complexation of ET-1 with BF 3 could signicantly tune and improve the sensitivity and response, particularly in the low water content range. To elucidate the mechanisms for the detection of water, 1 H NMR spectra of ET-1 and ET-1-BF 3 in CD 3 CN with and without 10 wt% of deuterated water were obtained (Fig. 7). The complexation with BF 3 signicantly shied the peaks of the aromatic protons, H a and H b , in ET-1 to the higher magnetic eld and those of the aromatic H c and H d to the lower eld, while the aliphatic protons were affected little ( Fig. 7a and b). 59 The addition of 10 wt% of D 2 O to the ET-1 solution, which generates ET-1-D 2 O as discussed above, caused large upeld peak shis of H a and H b close to the pyridinic nitrogen atom, a slight downeld shi of H c , and no shi of H d distant from the nitrogen atom (Fig. 7c). These changes are similar but lesser extents to the BF 3 complexation. In the ET-1-BF 3 solution with 10 wt% of D 2 O, the H d peak shied to the position close to those observed in the ET-1 solutions with and without 10 wt% of D 2 O (Fig. 7a and c), indicating the release of some BF 3 (Fig. 7d). The appearance of the H a , H b , and H c peaks between those of the ET-1 solution containing 10 wt% of D 2 O and the ET-1-BF 3 solution without D 2 O also supports the partial release. Therefore, the ET-1-BF 3 solution containing 10 wt% of D 2 O can be considered to be a mixture of ET-1-BF 3 , ET-1, and ET-1-D 2 O. Based on the results obtained in the photoabsorption, uorescence, and 1 H  NMR measurements and previous studies, 41,42,50-59 we proposed plausible mechanisms for the detection of water in organic solvent using ET-1-BF 3 in Fig. 8. In the region of low water content, a number of complex release BF 3 below ca. 10 wt%, 41,42 and the resultant ET-1 starts forming the hydrogen-bonded complex (ET-1-H 2 O) from ca. 1-2 wt%. [50][51][52][53][54][55][56][57][58] The ET-1-H 2 O forms over a wide range of water content. In the region of high water content above ca. 10 wt%, the hydrogen-bonded PTC (ET-1-H + ) gradually generates. [50][51][52][53][54][55][56][57][58] Previously, a photochromic dye sensor with intramolecular hydrogen bonding that can detect hydrogen bonding characters of media has been developed. 31 ET-1 detects water based on hydrogen bonding with water molecules similarly to the photochromic sensor. However, differently from the sensor, ET-1 stepwisely forms two complexes hydrogen-bonded with one water molecule or several water molecules, as the precursor 9-MP does. [50][51][52][53][54][55][56][57][58] Indeed, the responses of ET-1-BF 3 to water were demonstrated visually as shown in Fig. 8. The yellow color of the ET-1-BF 3 solution faded away with increasing water content due to the release of BF 3 and subsequent formation of ET-1-H 2 O, followed by the restoration of the yellow color as a result of the ET-1-H + formation. The uorescence color also changed in the order of light blue, blue, and green, together with the color changes.

Conclusions
We have developed ICT-type colorimetric and uorescence sensors, ET-1 and ET-1-BF 3 , for detection and determination of water over a wide range of the concentration in organic solvent. The sensors can response to water differently depending on the content. In the range of low water content (below ca. 10 wt%), ET-1-BF 3 releases BF 3 to generate ET-1, and ET-1 forms the hydrogen-bonded complex with one water molecule (ET-1-H 2 O).
In higher water contents (above ca. 10 wt%), the hydrogenbonded PTC (ET-1-H + ) gradually generates. Compared with the previous ICT-type sensors with b-carboline structure (9-MP and 9-MP-BF 3 ), the sensitivity and spectral response to water are signicantly improved over a wide concentration range by the fusion with the electron-donating juloidine and complexation with BF 3 . The juloidine conjugation enhances the basicity of the pyridinic nitrogen atom and the ICT characteristic. The BF 3 complexation contributes to the improvements particularly in the low water contents. This work shows a useful approach to tuning and improvement of optical sensors for sensitive detection and precise determination of water over various concentrations.

Conflicts of interest
There are no conicts to declare.