Substituent Effects on Dipicolinatooxovanadium(V) evaluated by NMR Spectroscopy Alejandro M. Trujillo, Jerome Burke, Debbie C. Crans* Department of Chemistry, Colorado State University, CO. 80523-1872, USA email: [email protected] 2,6-pyridinedicarboxylate: Hammett smeta vs. log(KX/KH) ABSTRACT: 1 -0.5 Hammett equation: log(KX/KH) = rs OH r = -0.5317x - 0.3974 r² = 0.04307 log (kX/kH) The effect of substituents on a vanadium-containing coordination complex was evaluated using linear free energy relationships and NMR spectroscopy. Substituents (H, OH, Cl, NH2 and NO2) on the tridentate ligand, 2,6-pyridinedicarboxylic acid in the 4-position allowed the generation of a Hammett plot.1 The data for the deprotonation reaction of the ligand resulted in a non-linear plot of log(KX/KH) as a function of the Hammett constant. When the 1H NMR chemical shift data (dX-dH) was plotted as function of the Hammett constant a similar non-linear plot was generated for both ligand and vanadium(V) complex. However, by using 51V NMR chemical shift data (dX - dH) and plotting against the Hammett constant, a linear correlation plot was obtained for dipicolinatooxovanadium(V) with an r2 of 88%. This data demonstrate the effectiveness of NMR chemical shifts for examining linear free energy relationships in metallo-organic compounds. 0.5 0 -0.3 -0.1 -0.5 NH H 0.1 0.3 0.5 0.7 0.9 NO2 2 -1 Dipicolinatooxovanadium(V): Hammett spara vs. -1.5 INTRODUCTION: -2 Cl smeta • Using the same experimental methodolgy as in figure 3, figure 4 illustrates the linear relationship of VO2[dipic-X]-. • The 1H NMR for the complex illustrates an increase in linear fit with an r2 = 38 % when plotted against the s values indicating an increase in the stability of the system. • The + c (c = 0.48) may indicate that there is stabilization of a negative charge centered around the oxovanadium group and stabilization of the complex by e- withdrawing substituents. NH2 Figure 2: A plot of the Hammett smeta constant plotted against the –logKa (logKX/KH) converted from pKa data from Smee et al forming 2,6-pyridinedicarboxylate. 9 7 51V NMR c = -6.6469x + 1.3761 r² = 0.88194 2 Dd = dX - dH Dd = dX - dH 5 • The slope r = -0.5 observed in figure 2 indicates an increase in the reaction rate and pulling e- away from the ring by the e- donating groups.11 3 OH 2 • The poor linear fit r = 4 % indicates the potential for a differing mechanism 1 H or the presence of resonance structures. -1 0 -1 -0.5 0.5 1 Cl NO 2 • The addition of a terms did not significantly improve the fit to the data (r = -3 4 % for x2). Figure 1: Chemical structure of pyridine-2,6-dicarboxylate and dipicolinatoxovanadium(V). The substituents used for -5 Hammett plots are of varying electronegativity (H, OH, Cl, NH2 and NO2) at the 4-position of the pyridine ring. • The red lines represent a possible alternative fit, where two competing spara • The use of 2,6-pyridinedicaroxylate (dipic) as a ligand for metal Figure 5: Plot of the Hammett spara constant plotted against the 51V NMR chemical shifts of mechanisms are present in the system. To support this interpretation, - in D O at pH ~3. The dipicolinatoxovanadium(V). Samples contained 20 mM dipicolinatoxovanadium(V) VO [dipic-X] 2,3,4,5 2 2 coordination complexes is widespread. additional substituents would need to be evaluated. samples were referenced to internal DSS on a 400 MHz NMR. • The resulting metal containing complexes have been used as anti-diabetic 51V NMR chemical shifts as shown in 1 • The creation of a Hammett plot using 2,6-pyridinedicarboxylic acid: Hammet s vs. H NMR 4,5 ortho agents when chelated to V(V) and Zn(II). figure 5, has not been previously attempted to the best of our knowledge. 0.5 c = -0.1218x - 0.3903 NMR adaptation tof the Hammett equation: • Here we analyze the substituent effects on the ligand, 2,651V chemical shift of the • The y-axis was produced by subtracting the r² = 0.0608 Δd = dX – dH = cs pyridinedicaroxylate and the V(V)-containing coordination complex, Cl H substituent d from the chemical shift of the parent complex d . X H 0 dipicolinatooxovanadium(V). -1 -0.5 0 0.5 1 1.5 2 2.5 3 • The slope of c = -6.6 indicates the effect of stabilization with e- donation. • Specifically we used a variety of Hammett plots and to evaluate the • This is a significantly different result from the 1H NMR study of figure 4. -0.5 substituent effects and the linear free energy relationships (LFERs) of the • The 51V NMR establishes a significant increase in the linear fit r2 = 88 %. ligand and metal complex. OH NH • By using a curved line (x2) the fit can be increased further to r2 = 99 %. • The 4-position of the pyridine ring of dipic has been referred to as the NO -1 CONCLUSIONS: sortho most significant position to study the substituent effects in dipic.6 Figure 3: A scatter plot where the Hammett sortho constants are plotted against the 1H NMR chemical shifts of • The deprotonation of 2,6-pyridinedicaroxylate does not produce a linear solutions containing 20 mM of 2,6-pyridinedicarboxylate (dipic-X) in D2O at ~pH 7. The samples were referenced to internal DSS. Will the ligand and complex have similar LFERs? relationship to the Hammett s values deviating from that of benzoic acid • Hammett plots have been generated previously using 1H and 13C NMR 1 and other systems. EXPERIMENTAL: chemical shifts.12 • The scatted data creates a system where differing reaction mechanisms Table 1: Information used for this poster. The Hammett s constants are provided for the ortho, meta and para • However this methodology is not probing a reaction as in figure 2, but the 1 51 may be present. positions. The –logKa, H and V chemical shifts are tabulated. effect of substituents on the resulting chemical shifts. (a) • The fit to two lines suggests the substituents exhibit differing degrees of Hammett s constant 2,6-dipic-X VO2[dipic-X] • The y-axis of figure 3 was generated by subtracting the substituent 51V (c) 1H aq (b) X s(ortho) s(meta) s(para) log(Kx/Ko) 1H (Ha) (b) resonance stabilization and differing LFERs. chemical shift dX from that of the parent dH (Δd = dX – dH). NH2 -0.33 -0.16 -0.66 -0.86 7.13 -524.71 7.24 • Metal chelation of the dipic ligand significantly increased the linear fit to • The slope c = -0.12 is consistent between figure 2 and 3 (-r), however the OH 0.89 0.12 -0.37 -0.46 7.10 -529.40 7.57 the Hammett s values using NMR spectroscopy. H 0.00 0.00 0.00 0.54 8.00 -532.13 8.34 fit r2 = 6 % is also poor. 51V NMR characterize the nature of the chelating • The findings using Cl 1.26 0.37 0.23 -1.76 8.05 -532.82 8.37 • The large r2 illustrates the limitations observed by Salmon et al. indicating pyridine nitrogen. NO2 2.03 0.71 0.78 0.00 7.30 -534.76 9.02 12 Hammett s vs. d/ppm plots can produces a poor fit in certain systems. (a) Hammett s values were obtained for pyridine with modification in the 4• This work illustrates a stabilization effect in 2,6-pyridinedicaroxylate position. through the V-N coordinate bond. Dipicolinatooxovanadium(V): Hammett sortho vs. 1H NMR 2 2 (b) Sample resonances were measured against DSS internally with D2O solvent. (c) Chemical shift resonances were measured against an external VOCl3 standard. NO2 0.5 Dd = dX - dH • Table 1 illustrates the values used for the following plots in this poster. • The Hammett s values used for this preliminary study are literature s values for the pyridine ring structure.7 • The s values may differ for the system due to the carboxyl groups at the 2 and 6 positions. • The logKa values represent the deprotonation reaction observed for the carboxyl groups (pKa2) illustrated in figure 2.8,9,10 • The 1H and 51V NMR chemical shift data are experimental data for samples 20 mM dipic-X and VO2[dipic-X]- in D2O at on a 400 MHz NMR. REFERENCES: c = 0.4803x - 0.8497 r² = 0.37891 1 0 -0.5 0H 0.5 1 2 Cl -0.5 -1 1.5 OH -1.5 NH2 -2 sortho Figure 4: Plot of the Hammett sortho constant plotted against the 1H NMR of 20 mM solution of dipicolinatoxovanadium(V) (VO2[dipic-X]-) in D2O at ~pH 3. The spectra were referenced against internal DSS. Note: The NH2 complex formed precipitates during acquisition; the resulting concentration is lower that 20 mM. 1. Hammett, L. P. J. Am. Chem. Soc., 1935, 59(1), 96. 6. Sakurai, H. ACS Symposium Series, 2007, 974, 110. 2. Lis, S., Hnatejko, Z., and Elbanowski, M. Bull. Pol. Acad. 7. Hansch, C., and Leo, A., Wiley-Interscience, N Y., 1979. Sci. Chem., 1994, 42(1), 49. 8. Smee, J.J. et al. J. Inorg. Biochem., 2009, 103, 575. 3. Germaine, G. R., and Murrel, W. G. Photochem. 9. Smee, J.J. et al. J. Inorg. Chem., 2007, 46, 9827. Photobiol., 1973, 17, 145. 10. Ooms, K. J. et. al. J. Inorg. Chem., 2007, 46, 9285. 4. Enyedy, E. A., Lakatos, A., Horvath, L., Kiss, T. J. Inorg. 11. Hopkinson, A. C. J. Chem. Soc. B 1969, 203. Biochem., 2008, 102, 1473. 12. Salmon, M., Jiminez, A., Salazar, I., and Zawadzki, R. J. 5. Crans, D. C., Trujillo, A. M., Pharazyn, P. S., Cohen, M. Chem. Ed., 1973, 50(5), 370 – 371. D. Coord. Chem. Rev. 2011, 255, 2178. ACKNOWLEDGMENTS: The authors would like to thank the support received from the Crans lab and the support from the staff at the CSU CIF. This work was funded in part by the CRC-NSF CHE 0244181 grant.