Design of a Dual Sensing Highly Selective Cyanide Chemodosimeter Based on Pyridinium ring Chemistry

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1 Design of a Dual Sensing Highly Selective Cyanide Chemodosimeter Based on Pyridinium ring Chemistry Sabir H. Mashraqui *a, Rupesh Betkar a, Mukesh Chandiramani a, Carolina Estarellas b, Antonio Frontera b a Department of Chemistry, University of Mumbai, Vidyanagari, Santacruz-E, Mumbai , India, b Department of Quimica, Universitat de les Illes Balears, Spain sh_mashraqui@yahoo.com Contents 1) 1 H NMR of compound 4 S1 2) 13 C NMR of compound 4 S2 3) Mass spectrum of compound 4 S3 4) 1 H NMR of Quino-P S4 5) 13 C NMR of Quino-P S5 6) Mass spectrum of Quino-P S6 7) 13 C NMR of Quino-P + KCN S7 8) Competitive Fluorescence Experiment S8 9) Job s plot S9 10) Limit of detection S10 11) D 2 O exchange and 1 H NMR studies S11-S13 12) Conformational analysis of Quino-P. S14 13) Reference S15 S0

2 1) 1 H NMR of compound 4 in CDCl 3 S1

3 2) 13 C NMR of compound 4 in CDCl 3 S2

4 3) Mass spectrum of compound 4. S3

5 4) 1 H NMR of Quino-P in 70:30 (v/v) DMSO-d 6 -D 2 O S4

6 5) 13 C NMR of Quino-P in 70:30 (v/v) DMSO-d 6 -D 2 O

7 S5 6) Mass spectrum of Quino-P. S6

8 7) 13 C NMR of Quino-P + KCN in 70:30 (v/v) DMSO-d 6 -D 2 O S7

9 8) Competitive Fluorescence Experiment: Competitive fluorescence studies were carried out by adding 2.5 x 10-4 M of TBACN to a aqueous DMSO solution of Quino-P (1 x 10-6 M) containing different anions such as Cl -, I -, Br -, SCN -, HSO 4 -, NO3 -, AcO -, F -, and H2 PO 4 - upto 2.5 x 10-3 M. 10 Emission Intensity anions Figure 1: Emission enhancement plot of Quino-P (1 x 10-6 M) in DMSO:H 2 O (7:3, v/v) in tris HCl, added anion in black bar at 2.5 x 10-3 M each; 1) Cl -, 2) Br -, 3) I -, 4) SCN , 5) HSO 4, 6) NO3, 7) AcO, 8) F - - -, 9) H 2 PO 4 and in presence of CN (2.5 x 10-4 M) in red bar. S8

10 9) Binding stoichiometry determination by Job s plot: For the calculation of Job s plot, the concentrations of the probe and TBACN is 10-4 M I x η CNη CN- Figure 2: Job s plot for Quino-P - CN - interaction by fluorescence response. S9

11 10) Limit of detection by using semilogarethemic method: The detection limit calculated using the semilogarithmic plot of F-F 0 /F 0 (where F 0 and F are emission intensities at 435 nm) against log [CN - ] was found to be 1.6 x10-6 M F-F 0 /F log [CN - μm] Figure 3: Determination of the detection limit of CN - with Quino-P. S10

12 11) 300 MHz 1 H NMR of Quino-P (Fig.4a) and after the D 2 O exchange (Fig.4b). Figure 4: a) 1 H NMR (300 MHz) of (a) Quino-P, (b) partial 1 H NMR of deuterium exchanged Quino-P, both spectra recorded in DMSO-d 6. D 2 O exchange experiment: The deuterium exchange of C2 and C6 protons was carried out as per the procedure reported by Foster, and Fyfe, 1 on N-methyl nicotinamide salt. Quino-P (7 mg) was added to a solution of D 2 O (1 ml) containing 0.1 ml of triethylamine. The reaction was stirred and heated to 90 o C for 10 h.then, the reaction was concentrated under high vacuum and further dried over KOH under vacuum for 4 h. The dried sample was used for recording the NMR shown above in Figure 4b. S11

13 1 H NMR assignments of Quino-P and Quino-P-cyano adduct Figure 5: a) 1 H NMR (300 MHz) of (a) Quino-P, (b) Quino-P + 5 equiv. of KCN, both spectra recorded in DMSO-d 6 -D 2 O (70:30, v/v). The protons assignments, shown in Figures 5a/5b are based on chemical shifts. spin multiplicity as well as deuterium exchange experiment. We mage a reasonable assumptions that a) the protons of the positively charged pyridinium ring in Quino-P would appear relatively downfield shifted compared to those of the neutral quinoline ring and b) the chemical shift of the pyridinium ring protons should follow the order H2>H6>H4>H5 based on their relative proximity to the positively charged nitrogen as well as to the substituent, quinoline ring. Accordingly, for free Quino-P, the downfield located resonances at δ 9.87 (singlet), δ 9.38 (doublet), δ 9.1 (doublet) and δ 8.29 (double doublet) have been respectively assigned to H2, H6, H4 and H5. The assigment of the signals at δ 9.87 and δ 9.38 to H2 and H6 respectively is supported on the ground that these signals almost completely vanished upon deuterium exchange experiment (see Figure 4). The remaining upfield located signals have been appropriately assigned to the quinoline ring protons (Figure 5a). After adding cyanide, the 1 H NMR (Figure 5b) revealed pronounced upfield shifts (δ 1.34 to 4.05) of all the pyridinium ring protons as well as the N-CH 3, because of the charge neutralization. Keeping their chemical shifts and multiplicities in mind, the upfield shifted singlet at δ 7.7 and a doublet at δ 6.15 could be assigned to the vinylic H2 and H6, respectively. S12

14 These signals are too downfield to be assignable to hydrogen located on a saturated sp 3 carbon to be formed upon cyanide addition. This obviously means that neither C2 nor C6 position is likely to be the site of cyanide attack. Consequently, the C4 position remains as the only viable position on which the cyanide addition could occur. In view of this, the signals at δ 5.05 (doublet) and 4.85 (double doublet) can be justifiably attributed to H4 and H5, respectively. Thus, the above 1 H NMR results confirm the formation of the C4-cyano-adduct with complete regioselectivity. S13

15 12) Conformational analysis of Quino-P. With a view to gaining insight on the cyanide interaction, we performed molecular modelling of Quino-P and its C4-cyano-adduct. Conformational analysis at the RI- BP86/TZVP level of theory generated global energy minimized conformer A and conformer B for Quino-P and Qiuno-P- CN- adduct, respectively (Fig. 5). It can be seen that for Quino-P, the dihedral angle, NCCC encompassing quinoline and the pyridinium nuclei is 17.9 degrees, while it is much reduced to 3.5 degrees in the corresponding cyano-adduct. Noteworthily, the nitrogen atom of the DHP ring of the cyano-adduct (conformer B) is almost coplanar with the conjugated quinoline ring. Moreover, an intramolecular H-bond is also established between the quinoline nitrogen atom and the acidic hydrogen alpha to the nitrile group (2.48 Å). The nearly coplanar conformation of the cyano-adduct implies a strong tendency towards π- conjugation between the DHP and the quinoline rings. To analyze the reactive electrophilic sites in Quino-P, we computed the excess positive charge on the C2, C4 and C6 of the pyridinium ring. As shown in Figure 6, the electrophilic reactivity follows the order C4>>C2>C6, a result that is in complete agreement with our experimental findings. Figure 6: Conformers, A and B are the lowest energy conformations of Quino-P and the Quino-P- CN- adduct, respectively. The conformer B shows an intramolecular H- bond (in Å). The structure C shows calculated charge densities (electron units) on C2, C4 and C6 of the pyridinium ring. S14

16 13. References: [1] R. Foster and C. A. Fyfe, Tetrahedron 1969, 25, S15