Letter - spectral assignment Received: 19 May 2014
Revised: 20 August 2014
Accepted: 21 August 2014
Published online in Wiley Online Library: 19 September 2014
(wileyonlinelibrary.com) DOI 10.1002/mrc.4145
The 1H, 13C, 15N, and 19F NMR chemical shifts assignments in 5,10,15-tris (pentafluorophenyl) tetra–15N corrole at 191 K Wojciech Bocian,a,b* Piotr Paluch,c Agnieszka Nowak-Król,a Daniel T. Gryko,a Marek Potrzebowski,c Justyna Śniechowska,c Jerzy Sitkowski,a,b Elżbieta Bednarekb and Lech Kozerskia,b Introduction
Sample preparation
Corroles[1] are aromatic tetrapyrrolic macrocycles closely related to porphyrins, both of which have 18 π-electrons in the main conjugation pathway. While the corrole literature is not as abundant as that of porphyrins, corrole chemistry dates back to the early 1960s when pieces of research were attempting to synthesize vitamin B12 analogs.[2] Unlike porphyrins, corroles have only three mesocarbon atoms and a direct pyrrole–pyrrole linkage. Additionally, corroles bear three interior N-pyrrolic protons, making the corrole a trianionic ligand when fully deprotonated; this feature makes these macrocycles capable of stabilizing metal ions with high oxidation states. While porphyrins and corroles have similar electronic structure, corroles exhibit some unique properties especially in terms of coordination chemistry,[3] photophysics,[4] and reactivity.[5] Because of its stability, 5,10,15-tris(pentafluorophenyl)corrole is the most popular object of the studies (Scheme 1).[6] The three NH protons in corroles, bearing three porphyrin like and one pyridine-type nitrogen atoms, undergo tautomerization inside the interior cavity. The assignments of the 1H resonances are therefore crucial for the elucidation of the tautomerization processes reflected in variable temperature 1H NMR spectra. However, the tautomerization processes affects the line shape of the signals in the spectra in the temperature range 325–190 K to the extent that individual assignments are impossible. With the aid of uniformly 15N-labeled corrole (Scheme 1), it was therefore undertaken in this account to assign all nuclei in a molecule, i.e., 1H, 13C, 15N, and 19F, at 191 K. We recently revealed that these assignments made it possible to elucidate the tautomerization process.[7] Although this process was recently studied in several laboratories ,[8,9] presented data challenge both spectral process assignments to physical processes in a molecule and the mechanism of tautomerization, which was never studied in detail. As mentioned in our prior work, the corrole even at low temperature of 191 K can exist in fast tautomeric equilibrium of two tautomers 1′ and 1″ (Fig. 5). The predominant tautomer 1′ is presented in Scheme 1.
The samples were prepared in toluene-d8 (99.8% + D) from Armar Chemicals. Solvent was dried with activated molecular sieves 4 Å. For experiments involving 19F, we used unlabeled samples with concentration ca 4 mg/ml. In all other experiments, we used 15N-labeled sample with concentration ca 10 mg/ml. The chemical shifts in 1H and 13C were referenced to the methyl group of toluene (2.09 and 21.3 ppm, respectively). The 15N chemical shifts were referenced to ammonia. The 19F chemical shifts were referenced to CFCl3.
Experimental
Magn. Reson. Chem. 2015, 53, 167–171
All 2D experiments were run on a 600-MHz Bruker Avance III spectrometer equipped with 1H, 13C, and 15N TXI probehead (1H-detected experiment) and 1H, 19F–109Ag BBOF probehead (19F and direct detected experiment), operating at 600.13, 564.69, 150.92, and 60.82 MHz for 1H, 19F, 13C, and 15N nuclei, respectively. 1 H–1H exchange spectroscopy (EXSY) was measured with mixing time of 100 ms. Sweep width in F1 and F2 was set to 2 ppm with offset centered at 8.66 ppm. In direct (F2) dimension, 512 points were acquired. The 128 rows with four transients per increment were collected. 1 H–15N HSQC was optimized for 1JHN = 92 Hz. Sweep width in F2 was set to 9.6 ppm with offset centered at 4.04 ppm; 1024 points were collected in this direct dimension. Sweep width in F1 was set to 100 ppm with offset centered at 145 ppm. The 128 rows were collected with two transients per increment. 1 H–15N HMBC was optimized for nJHN = 5 Hz and carried out without a low-pass J-filter. Sweep width in F2 was set to 2.4 ppm with offset centered at 8.75 ppm; 1024 points were collected in this
* Correspondence to: Wojciech Bocian, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. E-mail: [email protected] a Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw, Poland b National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland c Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
Copyright © 2014 John Wiley & Sons, Ltd.
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The details of synthesis are given in Supplementary Information.
NMR experiments
W. Bocian et al. function. This weighting function reproduces the experimentally observed population ratio of the two tautomers, and thus, obtained shieldings are in the best agreement with the experimental results. The 1J1H,15N and 2J15N,15N coupling constants were calculated using DFT B3PW91 functional and specialized pcJ-2 basis set.[11]
Results and Discussion The assignments presented do not require any presumptions and are based on information complemented from various homonuclear and heteronuclear NMR techniques.
Scheme 1. Structure of corrole tautomer 1′.
Proton resonance assignment The assignment of proton resonances in corrole, given in Fig. 1 and Table 1, is a nontrivial task because the system consists of four not connected, identical proton spin systems that can be unambiguously assigned using an experiment correlating neighboring pyrrole rings (i.e. with the help of a uniformly 13C-enriched parent corrole ring, otherwise as presented in this note) at low temperature. In this contribution, with the help of 15N-enriched corrole, using, based on 1 H–13C, 1H–15N, 1H–19F, 13C–19F scalar coupling and 1H–1H, 1H–19F, 19 19 F– F, exchange correlations, we were able to assign all nuclei in a molecule to the level of confidence that allowed to assign the mechanism of the proton tautomerization process.
1
13
15
19
Table 1. Chemical shift, δ ppm, of H, C, N, and F atoms in corrole macrocycles in toluene-d8 at 191 Ka 1
1
15
Figure 1. H NMR spectrum of corrole– N in toluene-d8 at 191 K and 15 600 MHz .The NH resonances show splittings because of N enrichment (Table 1).
direct dimension. Sweep width in F1 was set to 200 ppm with offset centered at 150 ppm. The 256 rows were collected with four transients per increment. 19 1 F– H HOESY was run with a mixing time of 200 ms. The experiment was carried without 1H decoupling during acquisition. Sweep width in F2 was set to 46.6 ppm with offset centered at 140 ppm; 2048 points were collected in this direct dimension. Sweep width in F1 was set to 2 ppm with offset centered at 8.5 ppm. The 96 rows were collected with 24 transients per increment. 19 F–19F NOESY/EXSY was measured with a mixing time of 100 ms. Sweep width in F1 and F2 was set to 46.6 ppm with offset centered at 140 ppm. In direct (F2) dimension, 4096 points were acquired. The 140 rows were collected with four transients per increment.
1
H
H2 H3 H7 H8 H12 H13 H17 H18 NH(AB) NH(C) NH(D)
δ ppm 9.007 8.684 8.969 8.680 8.336 8.570 7.989 8.503 0.024 6.357 6.294
Quantum chemical calculations
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Two tautomers of corrole 1′ and 1″ were built (Fig. 5), the corrole 1′ has protonated the NA, NC, and ND nitrogen while corrole 1″ has protonated the NB, NC, and ND nitrogen. Both tautomers were subjected to density functional theory (DFT) quantum chemical geometry optimizations at the Becke, three-parameter, Lee–Yang–Parr (B3LYP)/6-311 + G(d,p) level of theory with the use of the Gaussian 03 program package.[10] The chemical shielding calculations were conducted with the gauge including atomic orbital method using DFT B3LYP/6-311 + G(2d,p) method. The resulting NMR shieldings for the two structures were averaged with the use of a weighting
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13
15
Chemical shifts of H C and N atoms in corrole 13
C
δ ppm
C1 C2 C3 C4 C6 C7 C8 C9 C11 C12 C13 C14 C16 C17 C18 C19 C5-oAR C5-mAR C5-pAR C10-oAR C10-mAR C10-pAR C15-oAR C15-mAR C15-pAR
131.434 117.678 124.884 135.820 146.552 129.785 128.236 146.552 136.321 123.917 124.450 134.417 132.134 117.092 115.796 128.196 145.753 137.822 141.414 146.583 137.602 141.592 145.903 137.942 141.546
15
N
δ ppm
NA NB NC ND
172.920 211.074 120.900 125.662
19
δ ppm 138.502 160.859 151.473 137.845 161.229 151.473 138.951 160.564 151.163
F 5-F-oAR 5-F-mAR 5-F-pAR 10-F-oAR 10-F-mAR 10-F-pAR 15-F-oAR 15-F-mAR 15-F-pAR
a
Carbon atoms 5, 10, and 15 could not be observed in the HMBC spectrum because of significant broadening as a result of fluorine coupling.
Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2015, 53, 167–171
Corrole The 1H signal assignments involve identification of vicinal proton pairs and their assignments to a proper ring. The assignment of proton pair H17 and H18 is unambiguous because of the observation only on one of these (H17) longrange 6JH,F spin–spin couplings. The same concerns proton pair H2 and H3. The 1H–1H EXSY spectrum in Fig. 2 indicates that exchange correlates H7 with H13 and H8 with H12. Likewise, exchange correlates H17 with H3 and H18 with H2. On which ring these pairs reside is concluded from the 1H–15N HMBC spectrum in the succeeding texts. The assignment of proton pairs H12/13 and H7/8 involves 1 H/19F homonuclear and heteronuclear correlations. In the 19 F–19F NOESY/EXSY spectrum (Fig. 2, left) ortho-fluorine atoms in perfluorosubstituted phenyl at carbon C10 are easily identified because, because of the symmetry of the molecule, they do not undergo exchange with other fluorine atoms. Exchange cross peaks of ortho-fluorine atoms in subtituents on C5 and C15 carbon atoms are seen close to diagonal. This reasoning allows assignment of the H12 and H8 protons. In the spectrum 1 H–19F HOESY/EXSY (Fig. 2, center), it is seen that two signals do not give 1H–19F correlation. These are H2 and H18. Protons H12 and H8 give single correlation, and the rest give two correlations connected with exchange.
Heteronucleus resonance assignments in corrole ring The 13C proton-bearing carbon atoms in the corrole ring are identified in the 1H–13C HSQC spectrum and quaternary atoms in the 1H–13C HMBC spectrum (Supplementary Information).
19
The nitrogen atoms are assigned in 1H–15N HSQC and 1H–15N HMBC spectra (Fig. 3). Having established that H12 and H8 protons are in the vicinity of fluorine atoms in a perfluorophenyl ring substituted at carbon C10, it can be inferred from Fig. 3 (left) that a nitrogen atom at δ = 120.9 ppm, 1JN,H = 95.2 Hz, belongs to ring C. This chemical shift also identifies NH protons at the lowest frequency in the 1H–15N HSQC spectrum. That nitrogen atom cannot belong to ring B because it has a rather pyrrole character but not a pyridine character, as nitrogen NB. The reduced one-bond 1JN,H spin–spin couplings of nitrogen NB, δ = 211.07, 1JN,H = 18 Hz and NA, δ = 172.9, 1JN,H = 69.3 Hz points to a situation that the corrole is in a fast equilibrium of the two not equally populated tautomers 1′ and 1″, where the tautomer 1″ has deprotonated the NA nitrogen atom. On the other hand, the observation of the nitrogen–nitrogen coupling constant 2 JNA,NB = 9.6 Hz is explained by the fact that two nitrogen atoms are sharing one proton in a strong hydrogen bond of proton sponge type.[13] These spin–spin couplings are presented in Fig. 4 and Table 2. The X-ray structure of corrole shows that NH protons are located on rings A, C, and D.[12] It is worth noting that the observed J-coupling between nitrogen atoms NA and NB is the motionally averaged and populationweighted value of two J-couplings across strong hydrogen bonds: one between NA and NB in the tautomer where the sponge proton is bound to NA with a normal bond and to NB by a hydrogen bond (as in 1′) and that between NA and NB in the (less populated) tautomer where the sponge proton is bound to NB with a normal bond and to NA by a hydrogen bond (Fig. 5). As has already been mentioned, the averaging process described previously is too rapid to be evidenced in the line shape.
19
1
19
1
1
Figure 2. F– F NOESY/EXSY (left, expansions of diagonal signals are displayed), H– F HOESY/EXSY (center), and H– H NOESY/EXSY (right) spectra of corrole.
15
1
15
169
1
15
Figure 3. The H– N HMBC (left) and H– N HSQC (right) spectra of corrole– N at 191 K.
Magn. Reson. Chem. 2015, 53, 167–171
Copyright © 2014 John Wiley & Sons, Ltd.
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W. Bocian et al.
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Figure 4. Direct-observation N NMR spectra of corrole in toluene-d8 at 191 K. Spectrum a with proton decoupling and spectrum b with protons coupled.
Table 2. Experimentally measured and DFT-calculated coupling constants in corroles in Hza Coupling constants
Experimental Calculated corrole 1’
1
J NA-HA 1 J NB-HB 1 J NC-HC 1 J ND-HD 2 J NA-NB
69.3 18.0 95.2 93.6 9.6
92.9 4.6 96.7 94.2 9.2
Calculated Calculateda corrole 1” 76% 1′ + 24%1″ 4.5 95.1 90.6 98.0 8.9
69.5 19.3 95.2 95.1 9.1
a
Values for the 76 : 24 corrole tautomer ratio of 1′ : 1″.
Figure 6. Correlation of experimental chemical shifts of all assigned carbon atoms with calculated isotropic shielding constant values for the 76 : 24 corrole tautomer ratio of 1′ : 1″. Figure 5. One of the rate processes in corrole 1, assessed to remain very fast even at the lowest temperatures explored.
Assignments in perfluorosubstituents on C5, C10, and C15 carbon atoms These assignments are accomplished with the aid of 19F and 19F NOESY and EXSY, 1H and 19F HOESY, and 19F and 13C HSQC spectra (Figs. 5S, 6S and 7S in Supplementary Information).
agreement between the experiment and calculations is observed when the tautomer population of 1′ : 1″ is 76 : 24 . Using this tautomer ratio 76 : 24 as a weighting function to the DFT, calculated 13C isotropic shielding constants also give the best agreement with the experimental values (Fig. 6). The corresponding linear correlation coefficient is R1′ + 1″ = 0.9964, while the R coefficient values for the single tautomers 1′ and 1″ are respectively equal, R1′ = 0.9906 and R1″ = 0.8313.
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DFT calculations
Conclusion
Analyzing the experimental and calculated values of nitrogen chemical shifts and proton–nitrogen coupling constants (Table 2), we have deduced that both the unsymmetrical proton sponge NA..H.....NB and a fast tautomeric equilibrium exist. The best
Spectral assignments of all nuclei in the corrole macrocycle are crucial for a proper assessment of the dynamic processes involving four-site tautomerization of the three protons’ NH inside the interior of a macrocycle. These dynamic processes affect the line shapes
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2015, 53, 167–171
Corrole of NMR signals in a temperature range of 325 to 190 K making spectral assignments impossible in an intermediate exchange limit because of broadening of the signals. The assignments were only possible in a range of slow exchange limits, at ca 190 K. It was found that even at this temperature, exchange of a proton involved in an unsymmetrical proton sponge is still very fast. Here, we present the assignments of all nuclei in a corrole system accomplished by use of appropriate homonuclear and heteronuclear 1D and 2D experiments run on 15N-enriched molecules. The presented assignments of carbon chemical shifts and heteronuclear coupling constants are plausibly confirmed by DFT calculations. Acknowledgements The authors gratefully acknowledge the helpful discussions with Prof. Sławomir Szymański and his creative initiative during this study.
References [1] a) R. Paolesse, in The Porphyrin Handbook, vol. 2, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, New-York, 2000, pp. 201–232; b) J. L. Sessler, S. J. Weghorn, Expanded, Contracted & Isomeric Porphyrins, Pergamon, Oxford, 1997, pp. 11; c) C. Erben, S. Will, K. M. Kadish, in Porphyrin Handbook, vol. 2, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, San Diego, CA, 2000, p. 233; d) D. T. Gryko. Eur. J Org. Chem. 2002, 1735–1743; e) R. Guilard, J.-M. Barbe, C. Stern , K. M. Kadish, in The Porphyrin Handbook, vol.18, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, New-York, 2003, pp. 303–351; f) D. T. Gryko, J. P. Fox, D. P. Goldberg. J Porphyrins Phthalocyanines 2004, 8, 1091–1105; g) S. Nardis, D. Monti, R. Paolesse. Mini-Rev. Org. Chem. 2005, 2, 355–372; h) D. P. Goldberg. Acc. Chem. Res. 2007, 40, 626–634; i) I. Aviv, Z. Gross. Chem. Commun. 2007, 1987–1999. [2] A. W. Johnson, I. T. Kay. J Chem. Soc. 1965, 1620–1629. [3] a) W. Schöfberger, F. Lengwin, L. M. Reith, M. List, G. Knör. Inorg. Chem. Commun. 2010, 13, 1187–1190l; b) A. B. Alemayehu, A. Ghosh. J Porphyrins Phthalocyanines 2011, 15, 106–110; c) H. L. Buckley, W. A. Chomitz, B. Koszarna, M. Tasior, D. T. Gryko, P. J. Brothers, J. Arnold. Chem. Commun. 2012, 48, 10766–10768. [4] a) M. Tasior, D. T. Gryko, J. Shen, K. M. Kadish, T. Becherer, H. Langhals, B. Ventura, L. Flamigni. J Phys. Chem. C 2008, 112, 19699–19709; b) L. Flamigni, A. I. Ciuciu, H. Langhals, B. Böck, D. T. Gryko. Chem. Asian J 2012, 7, 582–592.
[5] a) S. Hiroto, K. Furukawa, H. Shinokubo, A. Osuka. J Am. Chem. Soc. 2006, 128, 12380; b) J. F. B. Barata, A. M. G. Silva, M. G. P. M. S. Neves, A. C. Tomé, A. M. S. Silva, J. A. S. Cavaleiro. Tetrahedron Lett. 2006, 47, 8171. [6] a) I. Luobeznova, M. Raizman, I. Goldberg, Z. Gross. Inorg. Chem. 2006, 45, 386–394; b) A. E. Meier-Callahan, H. B. Gray, Z. Gross. Inorg. Chem. 2000, 39, 3605–3607. [7] S. Szymański, P. Paluch, D. T. Gryko, A. Nowak-Król, W. Bocian, J. Sitkowski, M. Potrzebowski, L. Kozerski. Chem. Eur. J 2014, 20, 1720–1730. [8] Y. S. Balazs, I. Saltsman, A. Mahammed, E. Tkachenko, G. Golubkov, J. Levine, Z. Gross. Magn. Res. Chem. 2004, 42, 624–635. [9] M. Kruk, T. H. Ngo, P. Verstappen, A. Starukhin, J. Hofkens, W. Dehaen, W. Maes. J Phys. Chem. A 2012, 116, 10695–10703. [10] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision D.02, Gaussian, Inc., Wallingford CT, 2004. [11] F. Jensen. Theor. Chem. Acc. 2010, 126, 371. [12] Z. Gross, N. Galili, L. Simkhovich, I. Saltsman, M. Botoshansky, D. Bläser, R. Boese, I. Goldberg. Org. Lett. 1999, 1, 599–602. [13] a) R. W. Alder. Chem. Rev. 1989, 89, 1215–1223; b) V. Raab, E. Gauchenova, A. Merkoulov, K. Harms, J. Sundermeyer, B. Kovačević, Z. B. Maksić. J Am. Chem. Soc. 2005, 127, 15738–15743; c) J. F. Kögel, B. Oelkers, B. Kovačević, J. Sundermeyer. J Am. Chem. Soc. 2013, 135 (47), 17768–17774; d) M. Pietrzak, A. C. Try, B. Andrioletti, J. L. Sessler, P. Anzenbacher, H.-H. Limbach. Angew. Chem. Int. Ed. 2008, 47, 1123–1126.
Supporting Information Additional supporting information may be found in the online version of this article at the publisher’s website.
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Magn. Reson. Chem. 2015, 53, 167–171
Copyright © 2014 John Wiley & Sons, Ltd.
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Revised: 20 August 2014
Accepted: 21 August 2014
Published online in Wiley Online Library: 19 September 2014
(wileyonlinelibrary.com) DOI 10.1002/mrc.4145
The 1H, 13C, 15N, and 19F NMR chemical shifts assignments in 5,10,15-tris (pentafluorophenyl) tetra–15N corrole at 191 K Wojciech Bocian,a,b* Piotr Paluch,c Agnieszka Nowak-Król,a Daniel T. Gryko,a Marek Potrzebowski,c Justyna Śniechowska,c Jerzy Sitkowski,a,b Elżbieta Bednarekb and Lech Kozerskia,b Introduction
Sample preparation
Corroles[1] are aromatic tetrapyrrolic macrocycles closely related to porphyrins, both of which have 18 π-electrons in the main conjugation pathway. While the corrole literature is not as abundant as that of porphyrins, corrole chemistry dates back to the early 1960s when pieces of research were attempting to synthesize vitamin B12 analogs.[2] Unlike porphyrins, corroles have only three mesocarbon atoms and a direct pyrrole–pyrrole linkage. Additionally, corroles bear three interior N-pyrrolic protons, making the corrole a trianionic ligand when fully deprotonated; this feature makes these macrocycles capable of stabilizing metal ions with high oxidation states. While porphyrins and corroles have similar electronic structure, corroles exhibit some unique properties especially in terms of coordination chemistry,[3] photophysics,[4] and reactivity.[5] Because of its stability, 5,10,15-tris(pentafluorophenyl)corrole is the most popular object of the studies (Scheme 1).[6] The three NH protons in corroles, bearing three porphyrin like and one pyridine-type nitrogen atoms, undergo tautomerization inside the interior cavity. The assignments of the 1H resonances are therefore crucial for the elucidation of the tautomerization processes reflected in variable temperature 1H NMR spectra. However, the tautomerization processes affects the line shape of the signals in the spectra in the temperature range 325–190 K to the extent that individual assignments are impossible. With the aid of uniformly 15N-labeled corrole (Scheme 1), it was therefore undertaken in this account to assign all nuclei in a molecule, i.e., 1H, 13C, 15N, and 19F, at 191 K. We recently revealed that these assignments made it possible to elucidate the tautomerization process.[7] Although this process was recently studied in several laboratories ,[8,9] presented data challenge both spectral process assignments to physical processes in a molecule and the mechanism of tautomerization, which was never studied in detail. As mentioned in our prior work, the corrole even at low temperature of 191 K can exist in fast tautomeric equilibrium of two tautomers 1′ and 1″ (Fig. 5). The predominant tautomer 1′ is presented in Scheme 1.
The samples were prepared in toluene-d8 (99.8% + D) from Armar Chemicals. Solvent was dried with activated molecular sieves 4 Å. For experiments involving 19F, we used unlabeled samples with concentration ca 4 mg/ml. In all other experiments, we used 15N-labeled sample with concentration ca 10 mg/ml. The chemical shifts in 1H and 13C were referenced to the methyl group of toluene (2.09 and 21.3 ppm, respectively). The 15N chemical shifts were referenced to ammonia. The 19F chemical shifts were referenced to CFCl3.
Experimental
Magn. Reson. Chem. 2015, 53, 167–171
All 2D experiments were run on a 600-MHz Bruker Avance III spectrometer equipped with 1H, 13C, and 15N TXI probehead (1H-detected experiment) and 1H, 19F–109Ag BBOF probehead (19F and direct detected experiment), operating at 600.13, 564.69, 150.92, and 60.82 MHz for 1H, 19F, 13C, and 15N nuclei, respectively. 1 H–1H exchange spectroscopy (EXSY) was measured with mixing time of 100 ms. Sweep width in F1 and F2 was set to 2 ppm with offset centered at 8.66 ppm. In direct (F2) dimension, 512 points were acquired. The 128 rows with four transients per increment were collected. 1 H–15N HSQC was optimized for 1JHN = 92 Hz. Sweep width in F2 was set to 9.6 ppm with offset centered at 4.04 ppm; 1024 points were collected in this direct dimension. Sweep width in F1 was set to 100 ppm with offset centered at 145 ppm. The 128 rows were collected with two transients per increment. 1 H–15N HMBC was optimized for nJHN = 5 Hz and carried out without a low-pass J-filter. Sweep width in F2 was set to 2.4 ppm with offset centered at 8.75 ppm; 1024 points were collected in this
* Correspondence to: Wojciech Bocian, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. E-mail: [email protected] a Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw, Poland b National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland c Center of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
Copyright © 2014 John Wiley & Sons, Ltd.
167
The details of synthesis are given in Supplementary Information.
NMR experiments
W. Bocian et al. function. This weighting function reproduces the experimentally observed population ratio of the two tautomers, and thus, obtained shieldings are in the best agreement with the experimental results. The 1J1H,15N and 2J15N,15N coupling constants were calculated using DFT B3PW91 functional and specialized pcJ-2 basis set.[11]
Results and Discussion The assignments presented do not require any presumptions and are based on information complemented from various homonuclear and heteronuclear NMR techniques.
Scheme 1. Structure of corrole tautomer 1′.
Proton resonance assignment The assignment of proton resonances in corrole, given in Fig. 1 and Table 1, is a nontrivial task because the system consists of four not connected, identical proton spin systems that can be unambiguously assigned using an experiment correlating neighboring pyrrole rings (i.e. with the help of a uniformly 13C-enriched parent corrole ring, otherwise as presented in this note) at low temperature. In this contribution, with the help of 15N-enriched corrole, using, based on 1 H–13C, 1H–15N, 1H–19F, 13C–19F scalar coupling and 1H–1H, 1H–19F, 19 19 F– F, exchange correlations, we were able to assign all nuclei in a molecule to the level of confidence that allowed to assign the mechanism of the proton tautomerization process.
1
13
15
19
Table 1. Chemical shift, δ ppm, of H, C, N, and F atoms in corrole macrocycles in toluene-d8 at 191 Ka 1
1
15
Figure 1. H NMR spectrum of corrole– N in toluene-d8 at 191 K and 15 600 MHz .The NH resonances show splittings because of N enrichment (Table 1).
direct dimension. Sweep width in F1 was set to 200 ppm with offset centered at 150 ppm. The 256 rows were collected with four transients per increment. 19 1 F– H HOESY was run with a mixing time of 200 ms. The experiment was carried without 1H decoupling during acquisition. Sweep width in F2 was set to 46.6 ppm with offset centered at 140 ppm; 2048 points were collected in this direct dimension. Sweep width in F1 was set to 2 ppm with offset centered at 8.5 ppm. The 96 rows were collected with 24 transients per increment. 19 F–19F NOESY/EXSY was measured with a mixing time of 100 ms. Sweep width in F1 and F2 was set to 46.6 ppm with offset centered at 140 ppm. In direct (F2) dimension, 4096 points were acquired. The 140 rows were collected with four transients per increment.
1
H
H2 H3 H7 H8 H12 H13 H17 H18 NH(AB) NH(C) NH(D)
δ ppm 9.007 8.684 8.969 8.680 8.336 8.570 7.989 8.503 0.024 6.357 6.294
Quantum chemical calculations
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Two tautomers of corrole 1′ and 1″ were built (Fig. 5), the corrole 1′ has protonated the NA, NC, and ND nitrogen while corrole 1″ has protonated the NB, NC, and ND nitrogen. Both tautomers were subjected to density functional theory (DFT) quantum chemical geometry optimizations at the Becke, three-parameter, Lee–Yang–Parr (B3LYP)/6-311 + G(d,p) level of theory with the use of the Gaussian 03 program package.[10] The chemical shielding calculations were conducted with the gauge including atomic orbital method using DFT B3LYP/6-311 + G(2d,p) method. The resulting NMR shieldings for the two structures were averaged with the use of a weighting
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13
15
Chemical shifts of H C and N atoms in corrole 13
C
δ ppm
C1 C2 C3 C4 C6 C7 C8 C9 C11 C12 C13 C14 C16 C17 C18 C19 C5-oAR C5-mAR C5-pAR C10-oAR C10-mAR C10-pAR C15-oAR C15-mAR C15-pAR
131.434 117.678 124.884 135.820 146.552 129.785 128.236 146.552 136.321 123.917 124.450 134.417 132.134 117.092 115.796 128.196 145.753 137.822 141.414 146.583 137.602 141.592 145.903 137.942 141.546
15
N
δ ppm
NA NB NC ND
172.920 211.074 120.900 125.662
19
δ ppm 138.502 160.859 151.473 137.845 161.229 151.473 138.951 160.564 151.163
F 5-F-oAR 5-F-mAR 5-F-pAR 10-F-oAR 10-F-mAR 10-F-pAR 15-F-oAR 15-F-mAR 15-F-pAR
a
Carbon atoms 5, 10, and 15 could not be observed in the HMBC spectrum because of significant broadening as a result of fluorine coupling.
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Magn. Reson. Chem. 2015, 53, 167–171
Corrole The 1H signal assignments involve identification of vicinal proton pairs and their assignments to a proper ring. The assignment of proton pair H17 and H18 is unambiguous because of the observation only on one of these (H17) longrange 6JH,F spin–spin couplings. The same concerns proton pair H2 and H3. The 1H–1H EXSY spectrum in Fig. 2 indicates that exchange correlates H7 with H13 and H8 with H12. Likewise, exchange correlates H17 with H3 and H18 with H2. On which ring these pairs reside is concluded from the 1H–15N HMBC spectrum in the succeeding texts. The assignment of proton pairs H12/13 and H7/8 involves 1 H/19F homonuclear and heteronuclear correlations. In the 19 F–19F NOESY/EXSY spectrum (Fig. 2, left) ortho-fluorine atoms in perfluorosubstituted phenyl at carbon C10 are easily identified because, because of the symmetry of the molecule, they do not undergo exchange with other fluorine atoms. Exchange cross peaks of ortho-fluorine atoms in subtituents on C5 and C15 carbon atoms are seen close to diagonal. This reasoning allows assignment of the H12 and H8 protons. In the spectrum 1 H–19F HOESY/EXSY (Fig. 2, center), it is seen that two signals do not give 1H–19F correlation. These are H2 and H18. Protons H12 and H8 give single correlation, and the rest give two correlations connected with exchange.
Heteronucleus resonance assignments in corrole ring The 13C proton-bearing carbon atoms in the corrole ring are identified in the 1H–13C HSQC spectrum and quaternary atoms in the 1H–13C HMBC spectrum (Supplementary Information).
19
The nitrogen atoms are assigned in 1H–15N HSQC and 1H–15N HMBC spectra (Fig. 3). Having established that H12 and H8 protons are in the vicinity of fluorine atoms in a perfluorophenyl ring substituted at carbon C10, it can be inferred from Fig. 3 (left) that a nitrogen atom at δ = 120.9 ppm, 1JN,H = 95.2 Hz, belongs to ring C. This chemical shift also identifies NH protons at the lowest frequency in the 1H–15N HSQC spectrum. That nitrogen atom cannot belong to ring B because it has a rather pyrrole character but not a pyridine character, as nitrogen NB. The reduced one-bond 1JN,H spin–spin couplings of nitrogen NB, δ = 211.07, 1JN,H = 18 Hz and NA, δ = 172.9, 1JN,H = 69.3 Hz points to a situation that the corrole is in a fast equilibrium of the two not equally populated tautomers 1′ and 1″, where the tautomer 1″ has deprotonated the NA nitrogen atom. On the other hand, the observation of the nitrogen–nitrogen coupling constant 2 JNA,NB = 9.6 Hz is explained by the fact that two nitrogen atoms are sharing one proton in a strong hydrogen bond of proton sponge type.[13] These spin–spin couplings are presented in Fig. 4 and Table 2. The X-ray structure of corrole shows that NH protons are located on rings A, C, and D.[12] It is worth noting that the observed J-coupling between nitrogen atoms NA and NB is the motionally averaged and populationweighted value of two J-couplings across strong hydrogen bonds: one between NA and NB in the tautomer where the sponge proton is bound to NA with a normal bond and to NB by a hydrogen bond (as in 1′) and that between NA and NB in the (less populated) tautomer where the sponge proton is bound to NB with a normal bond and to NA by a hydrogen bond (Fig. 5). As has already been mentioned, the averaging process described previously is too rapid to be evidenced in the line shape.
19
1
19
1
1
Figure 2. F– F NOESY/EXSY (left, expansions of diagonal signals are displayed), H– F HOESY/EXSY (center), and H– H NOESY/EXSY (right) spectra of corrole.
15
1
15
169
1
15
Figure 3. The H– N HMBC (left) and H– N HSQC (right) spectra of corrole– N at 191 K.
Magn. Reson. Chem. 2015, 53, 167–171
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W. Bocian et al.
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Figure 4. Direct-observation N NMR spectra of corrole in toluene-d8 at 191 K. Spectrum a with proton decoupling and spectrum b with protons coupled.
Table 2. Experimentally measured and DFT-calculated coupling constants in corroles in Hza Coupling constants
Experimental Calculated corrole 1’
1
J NA-HA 1 J NB-HB 1 J NC-HC 1 J ND-HD 2 J NA-NB
69.3 18.0 95.2 93.6 9.6
92.9 4.6 96.7 94.2 9.2
Calculated Calculateda corrole 1” 76% 1′ + 24%1″ 4.5 95.1 90.6 98.0 8.9
69.5 19.3 95.2 95.1 9.1
a
Values for the 76 : 24 corrole tautomer ratio of 1′ : 1″.
Figure 6. Correlation of experimental chemical shifts of all assigned carbon atoms with calculated isotropic shielding constant values for the 76 : 24 corrole tautomer ratio of 1′ : 1″. Figure 5. One of the rate processes in corrole 1, assessed to remain very fast even at the lowest temperatures explored.
Assignments in perfluorosubstituents on C5, C10, and C15 carbon atoms These assignments are accomplished with the aid of 19F and 19F NOESY and EXSY, 1H and 19F HOESY, and 19F and 13C HSQC spectra (Figs. 5S, 6S and 7S in Supplementary Information).
agreement between the experiment and calculations is observed when the tautomer population of 1′ : 1″ is 76 : 24 . Using this tautomer ratio 76 : 24 as a weighting function to the DFT, calculated 13C isotropic shielding constants also give the best agreement with the experimental values (Fig. 6). The corresponding linear correlation coefficient is R1′ + 1″ = 0.9964, while the R coefficient values for the single tautomers 1′ and 1″ are respectively equal, R1′ = 0.9906 and R1″ = 0.8313.
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DFT calculations
Conclusion
Analyzing the experimental and calculated values of nitrogen chemical shifts and proton–nitrogen coupling constants (Table 2), we have deduced that both the unsymmetrical proton sponge NA..H.....NB and a fast tautomeric equilibrium exist. The best
Spectral assignments of all nuclei in the corrole macrocycle are crucial for a proper assessment of the dynamic processes involving four-site tautomerization of the three protons’ NH inside the interior of a macrocycle. These dynamic processes affect the line shapes
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Magn. Reson. Chem. 2015, 53, 167–171
Corrole of NMR signals in a temperature range of 325 to 190 K making spectral assignments impossible in an intermediate exchange limit because of broadening of the signals. The assignments were only possible in a range of slow exchange limits, at ca 190 K. It was found that even at this temperature, exchange of a proton involved in an unsymmetrical proton sponge is still very fast. Here, we present the assignments of all nuclei in a corrole system accomplished by use of appropriate homonuclear and heteronuclear 1D and 2D experiments run on 15N-enriched molecules. The presented assignments of carbon chemical shifts and heteronuclear coupling constants are plausibly confirmed by DFT calculations. Acknowledgements The authors gratefully acknowledge the helpful discussions with Prof. Sławomir Szymański and his creative initiative during this study.
References [1] a) R. Paolesse, in The Porphyrin Handbook, vol. 2, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, New-York, 2000, pp. 201–232; b) J. L. Sessler, S. J. Weghorn, Expanded, Contracted & Isomeric Porphyrins, Pergamon, Oxford, 1997, pp. 11; c) C. Erben, S. Will, K. M. Kadish, in Porphyrin Handbook, vol. 2, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, San Diego, CA, 2000, p. 233; d) D. T. Gryko. Eur. J Org. Chem. 2002, 1735–1743; e) R. Guilard, J.-M. Barbe, C. Stern , K. M. Kadish, in The Porphyrin Handbook, vol.18, (Eds: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, New-York, 2003, pp. 303–351; f) D. T. Gryko, J. P. Fox, D. P. Goldberg. J Porphyrins Phthalocyanines 2004, 8, 1091–1105; g) S. Nardis, D. Monti, R. Paolesse. Mini-Rev. Org. Chem. 2005, 2, 355–372; h) D. P. Goldberg. Acc. Chem. Res. 2007, 40, 626–634; i) I. Aviv, Z. Gross. Chem. Commun. 2007, 1987–1999. [2] A. W. Johnson, I. T. Kay. J Chem. Soc. 1965, 1620–1629. [3] a) W. Schöfberger, F. Lengwin, L. M. Reith, M. List, G. Knör. Inorg. Chem. Commun. 2010, 13, 1187–1190l; b) A. B. Alemayehu, A. Ghosh. J Porphyrins Phthalocyanines 2011, 15, 106–110; c) H. L. Buckley, W. A. Chomitz, B. Koszarna, M. Tasior, D. T. Gryko, P. J. Brothers, J. Arnold. Chem. Commun. 2012, 48, 10766–10768. [4] a) M. Tasior, D. T. Gryko, J. Shen, K. M. Kadish, T. Becherer, H. Langhals, B. Ventura, L. Flamigni. J Phys. Chem. C 2008, 112, 19699–19709; b) L. Flamigni, A. I. Ciuciu, H. Langhals, B. Böck, D. T. Gryko. Chem. Asian J 2012, 7, 582–592.
[5] a) S. Hiroto, K. Furukawa, H. Shinokubo, A. Osuka. J Am. Chem. Soc. 2006, 128, 12380; b) J. F. B. Barata, A. M. G. Silva, M. G. P. M. S. Neves, A. C. Tomé, A. M. S. Silva, J. A. S. Cavaleiro. Tetrahedron Lett. 2006, 47, 8171. [6] a) I. Luobeznova, M. Raizman, I. Goldberg, Z. Gross. Inorg. Chem. 2006, 45, 386–394; b) A. E. Meier-Callahan, H. B. Gray, Z. Gross. Inorg. Chem. 2000, 39, 3605–3607. [7] S. Szymański, P. Paluch, D. T. Gryko, A. Nowak-Król, W. Bocian, J. Sitkowski, M. Potrzebowski, L. Kozerski. Chem. Eur. J 2014, 20, 1720–1730. [8] Y. S. Balazs, I. Saltsman, A. Mahammed, E. Tkachenko, G. Golubkov, J. Levine, Z. Gross. Magn. Res. Chem. 2004, 42, 624–635. [9] M. Kruk, T. H. Ngo, P. Verstappen, A. Starukhin, J. Hofkens, W. Dehaen, W. Maes. J Phys. Chem. A 2012, 116, 10695–10703. [10] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision D.02, Gaussian, Inc., Wallingford CT, 2004. [11] F. Jensen. Theor. Chem. Acc. 2010, 126, 371. [12] Z. Gross, N. Galili, L. Simkhovich, I. Saltsman, M. Botoshansky, D. Bläser, R. Boese, I. Goldberg. Org. Lett. 1999, 1, 599–602. [13] a) R. W. Alder. Chem. Rev. 1989, 89, 1215–1223; b) V. Raab, E. Gauchenova, A. Merkoulov, K. Harms, J. Sundermeyer, B. Kovačević, Z. B. Maksić. J Am. Chem. Soc. 2005, 127, 15738–15743; c) J. F. Kögel, B. Oelkers, B. Kovačević, J. Sundermeyer. J Am. Chem. Soc. 2013, 135 (47), 17768–17774; d) M. Pietrzak, A. C. Try, B. Andrioletti, J. L. Sessler, P. Anzenbacher, H.-H. Limbach. Angew. Chem. Int. Ed. 2008, 47, 1123–1126.
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