Supplemental Information. Point-of-Use Detection of Amphetamine-Type. Stimulants with Host-Molecule-Functionalized. Organic Transistors

Transcription

1 Chem, Volume 3 Supplemental Information Point-of-Use Detection of Amphetamine-Type Stimulants with Host-Molecule-Functionalized Organic Transistors Yoonjung Jang, Moonjeong Jang, Hyoeun Kim, Sang Jin Lee, Eunyeong Jin, Jin Young Koo, In-Chul Hwang, Yonghwi Kim, Young Ho Ko, Ilha Hwang, Joon Hak Oh, and Kimoon Kim

2 The file includes: Section S1. Materials and general methods. Section S2. Characterization of ATS CB[7] complexes. Section S3. Synthesis and characterization of CB[7] derivatives. Section S4. X-ray crystal structure determination. Section S5. Electrical measurement. Figure S1. MALDI-TOF mass spectrum of 1 CB[7] complex. Figure S2. MALDI-TOF mass spectrum of 2 CB[7] complex. Figure S3. A representative ITC profile of 1 with CB[7] at 298 K in H 2 O. Figure S4. A representative ITC profile of 2 with CB[7] at 298 K in H 2 O. Figure S5. X-ray single crystal structures of 1 CB[7]. Figure S6. X-ray single crystal structures of 2 CB[7]. Figure S7. AFM images of the active layers of DDFTTF OFET-based sensors. Figure S8. Amphetamine (1) sensing results. Figure S9. Methamphetamine (2) sensing results. Figure S10. ATS sensing of OFET sensors in a synthetic urine. Figure S11. Current-voltage characteristics measured under ambient conditions. Figure S12. ATS sensing behaviors of a wireless OFET sensor functionalized with 4. Table S1. Association constants (K a ) and thermodynamic parameters for 1:1 host-guest binding between CB[7] and ATS obtained from ITC analyses. Legend for supplemental movies, S1 and S2. Other Supplemental Information for this manuscript includes the following: Movie S1. Smartphone display when the wireless OFET sensor was exposed to DI water and 1 pm of 1. Movie S2. Smartphone display when the wireless OFET sensor was exposed continuously to 1 pm of 1.

3 Section S1. Materials and general methods. All chemicals were used as received without further purification and all aqueous solutions were prepared with Millipore water. Synthetic urine (Surine TM #720) was purchased from Dyna-Tek industries (USA). Human urine for sensing experiments was collected from a healthy volunteer. ATS samples (1 and 2, racemic mixture) were purchased from Lipomed AG (Switzerland). Permission to use small quantities of ATS has been granted to K.K. by the Ministry of Food and Drug Safety, Republic of Korea (permission No. Daegu-120). All NMR spectra were recorded at ambient temperature using a Bruker AVANCE III HD 850 MHz spectrometer. Mass spectrometry was performed on an ABI 4700 Proteomics Analyser MALDI-TOF instrument. Isothermal titration calorimetery (ITC) experiments were performed on a VPITC (Microcal, Inc) at 298 K. Section S2. Characterization of ATS CB[7] complexes. The MALDI-TOF mass spectra and ITC experiments confirm the stable 1:1 inclusion complex formation between ATS and CB[7] [(1 CB[7] Cl)] + Intensity 15 [CB[7] + Na] m/z Exact Mass: [(1 CB[7] Cl)] + = Figure S1. MALDI-TOF mass spectrum of 1 CB[7] complex.

4 [(2 CB[7] Cl)] + 40 Intensity 20 [CB[7] + Na] Exact Mass: [(2 CB[7] Cl)] + = m/z Figure S2. MALDI-TOF mass spectrum of 2 CB[7] complex.

5 Figure S3. A representative ITC profile of 1 with CB[7] at 298 K in H 2 O. The best fitting was obtained from a model assuming 1:1 stoichiometry.

6 Figure S4. A representative ITC profile of 2 with CB[7] at 298 K in H 2 O. The best fitting was obtained from a model assuming 1:1 stoichiometry. Table S1. Association constants (K a ) and thermodynamic parameters for 1:1 hostguest binding between CB[7] and ATS obtained from ITC analyses. ATS K a (M -1 ) H (kj mol -1 ) T S (kj mol -1 ) 1 (1.2 ± 0.1) ± ± (8.1 ± 0.1) ± ± 0.5

7 Section S3. Synthesis and characterization of CB[7] derivatives. Cucurbit[7]uril (CB[7]) was purchased from CBTech ( HydroxyCB[7] and allyloxycb[7] (3) were synthesized based on a reported method (35). PhenylbutoxyCB[7] (4) was synthesized by following the procedure for the synthesis of 3 with slight modifications. To a solution of hydroxycb[7] (250 mg) in anhydrous DMSO (100 ml) was added sodium hydride (680 mg). The mixture was stirred for 12 h under an argon atmosphere, then 1-bromo-4-phenylbutane (2.0 g) was slowly added to the mixture and the mixture was further stirred for 12 h. After completion of the reaction, large amount of diethyl ether was added to the solution, then the solution was stirred and precipitate was washed with diethyl ether several times. The crude product was purified by recrystallization from diethyl ether and methanol (160 mg, 42%). The isolated product was a mixture of partially substituted phenylbutoxycb[7] with different degree of substitution. The NMR and mass data suggested that the degree of substitution ranges 4 6 with an average of ~5 phenylbutoxy groups per CB[7] molecule. 1 H NMR (850 MHz, DMSO-d 6 ): δ = (m, 8H), (m, 18H), 5.3 (br, 10H), 4.2 (br, 14H), (br, 3H), (br, 3H), (br, 6H); 13 C NMR (214 MHz, DMSO-d 6 ) δ = 155.7, 142.5, 128.4, 128.0, 126.3, 73.0, 71.7, 52.6, 35.8, 31.1, 28.6; MALDI-TOF: m/z (M = CB[7](phenylbutoxy) n (H) 14-n ) [M + MeOH + H] + : (n = 4), (n = 5), (n = 6); Elemental analysis data were calculated based on the average degree of substitution (n = 5) Anal. Calcd for (C 92 H 102 N 28 O 20 )(H 2 O) 8 (CH 3 OH) 1 Calcd: C, 53.3; H, 5.9; N, 18.7; Found: C, 53.0; H, 6.1; N, Section S4. X-ray crystal structure determination. Single crystals of ATS complexed with CB[7] suitable for X-ray work were obtained by the vapor-diffusion method. In order to obtain a single crystal of 1 complexed with CB[7], a mixture of CB[7] (5.0 mg) and 1 (1.0 mg; racemic mixture) was dissolved in 1.0 ml of water. A glass tube filled with the mixture was placed inside a larger vessel containing acetonitrile. In the case of a single crystal of 2 complexed with CB[7], a mixture of CB[7] (5.0 mg), 2 (1.2 mg; racemic mixture), NaH 2 PO 4 (1.0 mg) and H 3 PO 4 (3.0 L) was dissolved in 1.0 ml of water. A glass tube filled with the mixture was placed inside a larger vessel containing ethanol. In both cases, the outer vessel was sealed and kept in a vibration-free location at room temperature. The diffraction data for 1 CB[7] and 2 CB[7] were recorded on an ADSC Q210 CCD area detector with a synchrotron radiation (λ = Å) at 2D beamline in Pohang Accelerator Laboratory (PAL). The diffraction images were processed by using HKL3000. Absorption correction was performed by using the program PLATON. The structures were solved by direct methods (SHELXS-97) and refined by full-matrix least squares calculations on F 2 (SHELXL-97) using the WinGX program package. Since racemic mixtures of the drugs were used for crystallization, both R and S forms were observed in a 1:1 ratio in the host-guest complex structures (Figure S5 and S6). The 1 CB[7] and 2 CB[7] structures reported in this article have been deposited in the Cambridge Crystallographic Data Centre under accession number CCDC: and , respectively. 1 CB[7]: C 306 H 492 Cl 6 N 174 O 162, [(C 9 H 14 N ) (C 42 H 42 N 28 O 14 ) 4Cl ) (H 2 O) 13 ], Mr = , crystal dimensions mm 3, triclinic, P-1, a = (4) Å, b = (5) Å, c = (5) Å, α = 99.67(3), β =103.58(3), γ = (3), V = 10392(4) Å 3, T = 173 C, Z = 6, ρ calcd = g cm 3, μ = 10.6 cm 1, unique reflections out of with I>2σ(I), 2942 parameters, 1.49 < θ <20.49, R 1 = , wr 2 = , GOF = CB[7]: C 236 H 379 Na 2 N 116 O 139 P 6, [[(C 10 H 16 N ) (C 42 H 42 N 28 O 14 )] 4 ](C + ) 2 (H 2 PO 4 ) 6 (CH 3 CH 2 OH) 28 (H 2 O) 14 ], Mr = , crystal dimensions mm 3, hexagonal, P-3c1, a = (5) Å, c = (9) Å, α = 90.0(0), γ = 120.0(0), V = 54343(19) Å 3, T = 173 C, Z = 6, ρ calcd = g cm 3, μ = cm 1,

8 13005 unique reflections out of with I>2 σ(i), 2247 parameters, 1.40 < θ <20.51, R 1 = , wr 2 = , GOF = Figure S5. X-ray single crystal structures of 1 CB[7]. Since racemic mixture of 1 was used for crystallization, both (S)-1 CB[7] (A) and (R)-1 CB[7] (B) were observed in a 1:1 ratio in the host-guest complex structures. Hydrogen atoms of CB[7] are omitted for clarity. Figure S6. X-ray single crystal structures of 2 CB[7]. Since racemic mixture of 2 was used for crystallization, both (S)-2 CB[7] (A) and (R)-2 CB[7] (B) were observed in a 1:1 ratio in the host-guest complex structures. Hydrogen atoms of CB[7] are omitted for clarity. Section S5. Electrical measurement.

9 The electrical performance and sensing tests of OFETs were measured using a Keithley 4200 semiconductor parametric analyzer. The field-effect mobility ( FET ) was calculated in the saturated regime using the following equation: (1) where I D is the drain current, C g is the capacitance per unit area of the gate dielectric layer, and V GS and V TH are the gate voltage and threshold voltage, respectively. Figure S7. AFM images of the active layers of DDFTTF OFET-based sensors. (A) Height and (B) phase images of pristine DDFTTF 15 nm-thick film after thermal annealing at 150 C for 30 min under nitrogen conditions. (C) Height and (D) phase images of the surface of the 3-coated active layer.

10 Normalized current : 3/DDFTTF : DDFTTF DI water Time (sec) (s) Figure S8. Amphetamine (1) sensing results. Comparison of sensing responses of the sensors with and without 3 toward 1 pm of 1 at V DS = -2 V and V GS = -60 V. Sensitivity (I D /I D-BASE ) Concentration (M) Figure S9. Methamphetamine (2) sensing results. Plot shows the sensing of 2 with 3- functionalized sensors. The error bar represents the standard deviation.

11 Normalized current μm 0.2 nm nm 0.2 pm Artificial urine Urine Time Time (sec) (s) Figure S10. ATS sensing of OFET sensors in a synthetic urine. Sensing results of the sensors toward various concentrations of 1 in a synthetic urine solution at V DS = -2 V and V GS = -60 V. As clearly shown in the plot, the sensor having 4 layer detects 1 down to the sub-nm concentrations. -I D (A) V DS = -1.5V V GS (V) Figure S11. Current-voltage characteristics measured under ambient conditions. Transfer characteristics for flexible DDFTTF OFET-based sensors with 4 in p-channel operation mode.

12 pm of 1 Drain current (na) DI water Time Time (sec) (s) Rinsing Figure S12. ATS sensing behaviors of a wireless OFET sensor functionalized with 4. Wireless sensing curves of the ATS sensor toward 1 pm of 1 (V DS = -5 V and V GS = - 10 V). Rinsing step means the removal of the analyte solution from the sensor. The wireless OFET sensor exhibits the increased sensing signal when the device was exposed to 1 pm of 1. Also see movie S2.

13 Legend for supplemental movies Movie S1 Smartphone display when the wireless OFET sensor was exposed to DI water and 1 pm of 1. Description: DI water and 1 were added at 00:00:07 (Time, hours:minutes:seconds, total 1 min) and 00:00:28, respectively. The dropped analyte solution was removed at 00:00:47. The data reflect sensing signals shown in Figure S12. Movie S2 Smartphone display when the wireless OFET sensor was exposed continuously to 1 pm of 1. Description: The 1 solutions were added at 00:00:07 (Time, hours:minutes:seconds, total 00:02:16), 00:00:51 and 00:01:39. Sensing and removal of 1 solution were performed three times. The data reflect sensing signals shown in Figure 5E.