Synthesis of porphyrin-quinolone conjugates

Article abstract of DOI:10.1016/j.tetlet.2008.10.024

meso-Tetrakis(pentafluorophenyl)porphyrin reacts with propargyl alcohol to afford porphyrins substituted with one, two, three or four prop-2-yn-1-yloxy groups in the 4-position of the meso-aryl groups. These new porphyrin derivatives react with a 6-azidoquinolone under 'click-chemistry' conditions to give porphyrin-quinolone conjugates linked by 1,2,3-triazole units.

Full text of DOI:10.1016/j.tetlet.2008.10.024

Tetrahedron Letters 49 (2008) 7268–7270
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of porphyrin–quinolone conjugates
Fernanda da C. Santos a,b, Anna C. Cunha b, Maria Cecília B. V. de Souza b, Augusto C. Tomé a,
Maria G. P. M. S. Neves a, Vitor F. Ferreira b, José A. S. Cavaleiro a,
*
a University of Aveiro, Department of Chemistry, 3810-193 Aveiro, Portugal
b Universidade Federal Fluminense, Departamento de Química Orgânica, 24020-141 Niterói, Rio de Janeiro, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
meso-Tetrakis(pentafluorophenyl)porphyrin reacts with propargyl alcohol to afford porphyrins substi-
tuted with one, two, three or four prop-2-yn-1-yloxy groups in the 4-position of the meso-aryl groups.
These new porphyrin derivatives react with a 6-azidoquinolone under ‘click-chemistry’ conditions to give
porphyrin–quinolone conjugates linked by 1,2,3-triazole units.
Received 30 July 2008
Revised 1 October 2008
Accepted 6 October 2008
Available online 11 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Porphyrins
Triazoles
Quinolones
Click-chemistry
1. Introduction
active against viral diseases such as herpes simplex viruses10 and
fungal infections.11
Since the discovery of nalidixic acid, the parent compound of
the quinolone antibiotics, the molecular structures of quinolones
have been extensively modified to improve their pharmacologi-
cal properties and pharmacokinetic profiles.1–4 Quinolones are
easily synthesized, have a broad antimicrobial spectrum, are or-
ally and parenterally active and, apart from a few exceptions, are
non-toxic compounds. Therefore, they are important agents
against microbial pathogens. Ciprofloxacin and levofloxacin,
two quinolones introduced in 1986 and 1993, respectively, are
the most successful (economically and clinically) of all the to-
tally synthetic antimicrobial drugs.1 Quinolones are also being
considered for the treatment of fungal and viral5 infections and
for cancer chemotherapy.6 The antimicrobial activity of the quin-
olone derivatives is due to the inhibition of DNA synthesis by
targeting two essential topoisomerases: DNA gyrase and topoiso-
merase IV.1
Porphyrin derivatives are also exhibiting several medicinal
applications, namely as photosensitizers in the photodynamic
therapy (PDT) of cancer diseases, in the treatment of age-related
macular degeneration, and in the diagnosis of neoplastic diseases.7
Porphyrins are also very effective against bacteria and viruses and
are currently being studied for the photodynamic inactivation of
pathogenic microorganisms.8,9 For example, porphyrins are highly
The emergence of antibiotic resistance among pathogenic bac-
teria has led to a major research effort to find alternative antibac-
terial therapeutics. In this context, the synthesis of molecules with
dual functions may be a good strategy for the discovery of new
drugs. Those molecules can be achieved by coupling entities con-
taining well-established pharmacological activities. Frequently,
the resulting dyad systems have improved biochemical character-
istics relatively to their components or even new biological proper-
ties.12 With this in mind, we have designed a synthetic route to
porphyrin–quinolone conjugates which involves the 1,3-dipolar
cycloaddition of an azidoquinolone to porphyrins bearing alkynyl
groups. It is expected that the new conjugates will display interest-
ing biological activities.
This Letter describes the synthesis of five novel porphyrin–
quinolone conjugates (5a–d) linked by 1,2,3-triazole units. Four
novel porphyrins bearing one to four prop-2-yn-1-yloxy groups
in the 4-position of the meso-aryl substituents (2a–d) were pre-
pared and their reaction with 6-azidoquinolone 4, under ‘click-
chemistry’ conditions, afforded the corresponding new porphy-
rin–triazole–quinolones 5a–d. Typically this type of reaction leads
to a mixture of isomeric 1,4- and 1,5-disubstituted 1,2,3-triazoles13
but the copper(I)-catalyzed variant affords selectively the 1,4-
disubstituted derivatives.14–16 This ‘click-chemistry’17 reaction is
especially interesting, since it can be conducted under mild condi-
tions, in various solvents, and generally affords high yields of the
expected triazoles.
* Corresponding author. Tel.: +351 234 370 717; fax: +351 234 370 084.
E-mail address: jcavaleiro@ua.pt (J. A. S. Cavaleiro).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.024

Fernanda da C. Santos et al. / Tetrahedron Letters 49 (2008) 7268–7270
7269
Table 1
Synthesis of triazoles 5a–d
2. Results and discussion
For the synthesis of the new porphyrin derivatives we started
with the simple and symmetric meso-tetrakis(pentafluorophe-
nyl)porphyrin (1), easily obtained from pentafluorobenzaldehyde
and pyrrole under microwave irradiation.18 The reaction of por-
phyrin 1 with an excess (10 equiv.) of propargyl alcohol in DMSO,
in the presence of potassium carbonate, for 24 h at 80 °C, affords
the tetrasubstituted porphyrin 2d in 65% yield along with a mix-
ture of the di- and tri-substituted porphyrins 2b–c (Scheme 1).
These compounds were separated by column chromatography (sil-
ica gel) using chloroform/petroleum ether (1:3) as the eluent.19
The formation of the mono-substituted derivative 2a was opti-
mized to 86% yield by using an excess of porphyrin 1 relatively
to propargyl alcohol (3:1 molar equiv.). In this case, the reaction
was carried out at 50 °C for 4 h; minor amounts of disubstituted
products were also formed.
Alkyne
Azidoquinolone 4
(number of equiv)
Reaction time (h)
Triazole 5
(isolated yields, %)
3a
3b + 3b0
3c
2
4
6
8
8
93
88
62
53
48
48
72
3d
oxy group (Table 1).22 The cycloadducts were purified by prepara-
tive TLC. The isolated yields of the triazole derivatives are in the
range 53–93%, being the best result for the monotriazole deriva-
tive. Ditriazole derivatives were obtained in a global 88% yield as
a mixture of isomers 5b and 5b0, which could be separated by pre-
parative TLC. As expected, the slowest reaction, and the lowest
yield (53%), was for the formation of the tetratriazole derivative
5d.23
The structures of compounds 5a–d were confirmed by their
mass, 1H and 19F NMR spectra.24 Compound 5a was also character-
ized by 13C NMR. Typically, their 1H NMR spectra (in DMSO-d6)
show multiplets in the range of d 9.22–9.17 ppm corresponding
to the b-pyrrolic protons. The quinolone protons H-20 and H-50 ap-
pear as broad signals in the range of d 8.82–8.79 ppm, while the
proton of the triazole ring (H-500) appears as a singlet in the range
of d 9.48–9.47 ppm. This pattern is observed for all compounds 5a–
d. The ESI mass spectra of compounds 5a–c show the [M+Na]+ ion
while the spectrum of 5d shows the [M+2Na]2+ ion.
All porphyrin derivatives 2a–d were fully characterized by 1H
and 19F NMR and high resolution mass spectrometry. The 1H
NMR spectra of these compounds show typically two singlets at
d 5.23 and 2.82 ppm corresponding to the resonances of the –
OCH2– and –C„CH protons, respectively.
The formation of the porphyrin–quinolone conjugates involves
the 1,3-dipolar cycloaddition reaction of the propynyloxy groups
in derivatives 2a–d with the 6-azidoquinolone 420,21 under ‘click-
chemistry’ conditions, that is, using copper sulfate and ascorbic
acid as catalyst.15 However, since free-base porphyrins are metal-
lated by copper, it was necessary to prepare, previously, the zinc
complexes 3a–d. These complexes were obtained in quantitative
yields from the reaction of 2a–d with zinc acetate in a 2:1 mixture
of chloroform/methanol at 50 °C for 15 min.
In conclusion, a versatile route to new porphyrin–triazole–quin-
olone derivatives 5a–d is described. It involves the nucleophilic
displacement of fluorine atoms in porphyrin 1 by reaction with
propargyl alcohol, metallation with zinc acetate, and reaction with
the 6-azidoquinolone 4 under ‘click-chemistry’ conditions. Further
The cycloaddition reactions were carried out in DMF, at 50 °C,
for 4–48 h, using 2 equiv. of 6-azidoquinolone 4 for each propynyl-
F
F
F
F
R3
F
F
O
F
HN
F
F
F
F
NH
F
F
F
F
F
F
N
N
N
F
F
F
F
F
F
a)
N
M
N
N
a, R1 = R2 = R3 = F
F
F
1
, R = OCH2CCH; R2 = R3 = F
b
F
F
F
2
, R = OCH2CCH; R1 = R3 = F
b'
F
F
c, R1 = R2 = OCH2CCH; R4 = F
F
F
R2
R1
1
2
, R = R = R3 = OCH2CCH
d
F
F
F
F
1
2
3
, X = 2H
O
b)
2+
N3
CO2Et
c)
, X = Zn
N
Et
4
N
O
N
4''
5'
4'
CO2Et
N
F
F
3'
2'
R3
5''
O
7'
F
F
N
Et
8'
F
F
N
F
F
F
F
N
Zn
N
N
a, R1 = R2 = R3 = F
O
N
N
, R1 = X; R2 = R3 =F
CO2Et
b
N
F
F
b', R2 = X; R1 = R3 = F
c, R1= R2 = X; R4 = F
O
F
F
X=
N
Et
R2
R1
, R1 = R2 = R3 = X
F
F
5
d
Scheme 1. Reagents and conditions: (a) propargyl alcohol, K2CO3, DMSO, 50 °C or 80 °C; (b) Zn(OAc)2ꢀ5H2O, CHCl3/MeOH 2:1, 50 °C (100%); (c) CuSO4ꢀ5H2O, ascorbic acid,
DMF, 50 °C, 8–72 h.

7270
Fernanda da C. Santos et al. / Tetrahedron Letters 49 (2008) 7268–7270
DMF (3 mL) and CuSO4ꢀ5H2O (0.03–0.12 mmol) and ascorbic acid (0.06–
0.24 mmol) were added. The reaction mixture was stirred at 50 °C until the
disappearance of the starting porphyrin (8–72 h, monitored by TLC). After
cooling to room temperature, the mixture was diluted with chloroform and
washed with water (3 ꢁ 5 mL). The solvent was evaporated under reduced
pressure and the residue was purified by preparative TLC using
dichloromethane/ethanol (20:1) as the eluent. Compounds 5a–d were
crystallized from ethanol.
studies on the properties of these new porphyrin derivatives are
currently under investigation in our laboratories.
Acknowledgements
Thanks are due to CNPq-Brazil and to CAPES (Brazil)-GRICES/
FCT (Portugal) joint protocol for funding. Thanks are also due to
the University of Aveiro Organic Chemistry Research Unit, and F.
C. Santos thanks that protocol for her six months grant at Aveiro.
23. Recently,
a similar system was used to prepare porphyrin-b-cyclodextrin
conjugates Liu, Y.; Ke, C.-F.; Zhang, H.-Y.; Cui, J.; Ding, F. J. Am. Chem. Soc. 2008,
130, 600–605.
24. Compound 5a: mp >300 °C; 1H NMR (300.13 MHz, DMSO-d6, internal
standard: Me4Si): d = 1.31 (t, J = 7.1 Hz, 3H, CO2CH2CH3), 1.42 (t, J = 6.8 Hz,
3H, NCH2CH3), 4.27 (q, J = 7.1 Hz, 2H, CO2CH2CH3), 4.51 (q, J = 6.8 Hz, 2H,
NCH2CH3), 5.82 (s, 2H, OCH2-triazole), 8.16 (d, J = 9.2 Hz, 1H, H-80), 8.47
(dd, J = 2.0 and 9.2 Hz, 1H, H-70), 8.82 (br s, 2H, H-20 and H-50), 9.22 (m,
8H, H-b), 9.48 (s, 1H, H-500); 19F NMR (282.38 MHz, DMSO-d6, external
standard: C6F6 at ꢂ163 ppm): d = ꢂ185.51 to ꢂ185.44 (m, 6F, F-meta),
ꢂ179.57 to ꢂ179.50 (m, 2F, F-meta), ꢂ175.75 (t, J = 22.6 Hz, 3F, F-para),
ꢂ161.78 (dd, J = 7.6 and 23.1 Hz, 2F, F-ortho), ꢂ160.28 (dd, J = 7.6 and
References and notes
1. Mitscher, L. A. Chem. Rev. 2005, 105, 559–592.
2. Andersson, M. I.; MacGowan, A. P. J. Antimicrob. Chemother. 2003, 51, 1–11.
3. Van Bambeke, F.; Michot, J.-M.; Van Eldere, J.; Tulkens, P. M. Clin. Microbiol.
Infect. 2005, 11, 256–280.
4. Ball, P. J. Antimicrob. Chemother. 2000, 46, 17–24.
23.1 Hz, 6F, F-ortho); UV–vis (DMSO): kmax (loge) = 324 (4.3), 422 (5.3), 551
5. (a) Ohmine, T.; Katsube, T.; Tsuzaki, Y.; Kazui, M.; Kobayashi, N.; Komai, T.;
Hagihara, M.; Nishigaki, T.; Iwamoto, A.; Kimura, T.; Kashiwase, H.; Yamashita,
M. Bioorg. Med. Chem. Lett. 2002, 12, 739–742; (b) Brideau, R. J.; Knechtel, M. L.;
Huang, A.; Vaillancourt, V. A.; Vera, E. E.; Oien, N. L.; Hopkins, T. A.; Wieber, J. L.;
Wilkinson, K. F.; Rush, B. D.; Schwende, F. J.; Wathen, M. W. Antiviral Res. 2002,
54, 19–28; (c) Souza, T. M. L.; Cirne-Santos, C. C.; Rodrigues, D. Q.; Abreu, C. M.;
Tanuri, A.; Ferreira, V. F.; Marques, I. P.; Souza, M. C. B. V.; Fontes, C. F. L.;
Frugulhetti, I. C. P. P.; Bou-Habib, D. C. Curr. HIV Res. 2008, 6, 209–217.
6. Chu, D. T.; Hallas, R.; Clement, J. J.; Alder, J.; McDonald, E.; Plattner, J. J. Drugs
Exp. Clin. Res. 1992, 18, 275–282.
7. The Porphyrin Handbook; Kadish, K., Smith, K. M., Guilard, R., Eds.; Academic
Press: New York, 2000; Vol. 6,.
8. Wainwright, M. J. Antimicrob. Chemother. 1998, 42, 13–28.
9. Costa, L.; Alves, E.; Carvalho, C. M. B.; Tomé, J. P. C.; Faustino, M. A. F.; Neves, M.
G. P. M. S.; Tomé, A. C.; Cavaleiro, J. A. S.; Cunha, Â.; Almeida, A. Photochem.
Photobiol. Sci. 2008, 7, 415–422. and references cited therein.
10. Tomé, J. P. C.; Silva, E. M. P.; Pereira, A. M. V. M.; Alonso, C. M. A.; Faustino, M. A.
F.; Neves, M. G. P. M. S.; Tomé, A. C.; Cavaleiro, J. A. S.; Tavares, S. A. P.; Duarte,
R. R.; Caeiro, M. F.; Valdeira, M. L. Bioorg. Med. Chem. 2007, 15, 4705–4713.
11. Donnelly, R. F.; McCarron, P. A.; Tunney, M. M. Microbiol. Res. 2008, 163, 1–12.
12. (a) Zhao, G.; Miller, M. J.; Franzblau, S.; Wan, B.; Möllmann, U. Bioorg. Med.
Chem. Lett. 2006, 16, 5534–5537; (b) Srivastava, B. K.; Solanki, M.; Mishra, B.;
Soni, R.; Jayadev, S.; Valani, D.; Jain, M.; Patel, P. R. Bioorg. Med. Chem. Lett.
2007, 17, 1924–1929; (c) Wang, J.; Huang, J.; Wu, Y.; Hai, L.; Wang, G. Lett. Org.
Chem. 2008, 5, 336–341.
13. Tomé, A. C. 1,2,3-Triazoles. In Science of Synthesis—Houben–Weyl Methods of
Molecular Transformations; Storr, R. C., Gilchrist, T. L., Eds.; Thieme: Stuttgart,
2004; Vol. 13,.
14. Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064.
15. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. 2002,
114, 2708–2711; . Angew. Chem., Int. Ed. 2002, 41, 2596–2599.
16. For a recent review on 1,3-dipolar cycloadditions of azides and alkynes see
Lutz, J.-F. Angew. Chem., Int. Ed 2007, 46, 1018–1025.
(4.1) nm; HRMS (ESI) m/z calcd for C61H25F19N8O4ZnNa [M+Na]+ 1381.0885,
found 1381.0834.
Compound 5b: mp >300 °C; 1H NMR (300.13 MHz, DMSO-d6, internal
standard: Me4Si): d = 1.30 (t, J = 7.1 Hz, 6H, CO2CH2CH3), 1.42 (t, J = 7.0 Hz,
6H, NCH2CH3), 4.26 (q, J = 7.1 Hz, 4H, CO2CH2CH3), 4.50 (q, J = 7.0 Hz, 4H,
NCH2CH3), 5.81 (s, 4H, OCH2-triazole), 8.15 (d, J = 9.0, 2H, H-80), 8.45 (dd,
J = 2.5 and 9.0 Hz, 2H, H-70), 8.81 (br s, 4H, H-20 and H-50), 9.22 and 9.18
(d, J = 3.4 Hz, 8H, H-b), 9.47 (s, 2H, H-500); 19F NMR (282.38 MHz, DMSO-d6,
external standard: C6F6 at ꢂ163 ppm): d = ꢂ186.69 (dd, J = 5.6 and 28.2 Hz,
4F, F-meta), ꢂ180.10 (dd, J = 8.5 and 28.2 Hz, 4F, F-meta), ꢂ177.99 (t,
J = 22.6 Hz, 2F, F-para), ꢂ164.13 (dd, J = 5.6 and 25.4 Hz, 4F, F-ortho),
ꢂ162.78 (dd, J = 5.6 and 28.2 Hz, 4F, F-ortho); UV–vis (DMSO): kmax
(loge) = 325 (4.5), 421 (5.4), 551 (4.1) nm; HRMS (ESI) m/z calcd for
C78H42F18N12O8ZnNa [M+Na]+ 1703.2145, found 1703.2098.
Compound 5b0: mp >300 °C; 1H NMR (300.13 MHz, DMSO-d6, internal
standard: Me4Si): d = 1.31 (t, J = 7.0 Hz, 6H, CO2CH2CH3), 1.42 (t, J = 6.9 Hz,
6H, NCH2CH3), 4.27 (q, J = 7.0 Hz, 4H, CO2CH2CH3), 4.51 (q, J = 6.9 Hz, 4H,
NCH2CH3), 5.81 (s, 4H, OCH2-triazole), 8.16 (d, J = 9.1 Hz, 2H, H-80), 8.45
(dd, J = 2.8 and 9.1 Hz, 2H, H-70), 8.81 (br s, 4H, H-20 and H-50), 9.23 and
9.18 (d, J = 4.7 Hz, 8H, H-b), 9.47 (s, 2H, H-500); 19F NMR (282.38 MHz,
DMSO-d6, external standard: C6F6 at ꢂ163 ppm): d = ꢂ186.69 (dd, J = 5.6
and 28.2 Hz, 4F, F-meta), ꢂ180.10 (dd, J = 8.5 and 28.2 Hz, 4F, F-meta),
ꢂ177.99 (t, J = 22.6 Hz, 2F, F-para), ꢂ164.13 (dd, J = 5.6 and 25.4 Hz, 4F, F-
ortho), ꢂ162.78 (dd, J = 5.6 and 28.2 Hz, 4F, F-ortho); UV–vis (DMSO): kmax
(loge) = 327 (4.5), 421 (5.5), 551 (4.1) nm; HRMS (ESI) m/z calcd for
C78H42F18N12O8ZnNa [M+Na]+ 1703.2145, found 1703.2077.
Compound 5c: mp >300 °C; 1H NMR (300.13 MHz, DMSO-d6, internal
standard: Me4Si): d = 1.30 (t, J = 7.1 Hz, 9H, CO2CH2CH3), 1.42 (t, J = 6.8 Hz,
9H, NCH2CH3), 4.27–4.24 (m, 6H, CO2CH2CH3), 4.51–4.49 (m, 6H, NCH2CH3),
5.82 (s, 6H, OCH2-triazole), 8.14 (d, J = 9.2 Hz, 3H, H-80), 8.45 (dd, J = 2.4 and
9.2 Hz, 3H, H-70), 8.79 (br s, 6H, H-20 and H-50), 9.21–9.17 (m, 8H, H-b), 9.47
(s, 3H, H-500); 19F NMR (282.38 MHz, DMSO-d6, external standard: C6F6 at
ꢂ163 ppm): d = ꢂ186.69 (dd, J = 8.5 and 31.0 Hz, 2F, F-meta), ꢂ180.09 (dd,
J = 8.5 and 31.0 Hz, 6F, F-meta), ꢂ178.00 (t, J = 22.6 Hz, 1F, F-para), ꢂ164.13
(dd, J = 8.5 and 31.0 Hz, 6F, F-ortho), ꢂ162.77 (dd, J = 8.5 and 31.0 Hz, 2F, F-
17. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021.
18. De Paula, R.; Pinto, D.; Faustino, M. A.; Neves, M. G. P. M. S.; Cavaleiro, J. A. S. J.
Heterocycl. Chem. 2008, 45, 453–459.
ortho); UV–vis (DMSO): kmax (log e) = 340 (4.6), 422 (5.5), 551 (4.1) nm;
HRMS (ESI) m/z calcd for C95H59F17N16O12ZnNa [M+Na]+ 2025.3411, found
2025.3376.
19. It was not possible to separate isomers 2b and 2b0. The mixture was used in the
cycloaddition reaction with the azidoquinolone 4, yielding
a mixture of
Compound 5d: mp >300 °C; 1H NMR (300.13 MHz, DMSO-d6, internal
standard: Me4Si): d = 1.30 (t, J = 7.1 Hz, 12H, CO2CH2CH3), 1.42 (t,
J = 7.0 Hz, 12H, NCH2CH3), 4.26 (q, J = 7.1 Hz, 8H, CO2CH2CH3), 4.51–4.49
(m, 8H, NCH2CH3), 5.83 (s, 8H, OCH2-triazole), 8.14 (d, J = 9.2, 4H, H-80), 8.45
(dd, J = 2.6 and 9.2 Hz, 4H, H-70), 8.79 (br s, 8H, H-20 and H-50), 9.17 (s, 8H,
H-b), 9.48 (s, 4H, H-500); 19F NMR (282.38 MHz, DMSO-d6, external standard:
C6F6 at ꢂ163 ppm) d = ꢂ179.15 (dd, J = 11.3 and 25.4 Hz, 8F, F-meta),
ꢂ161.82 (dd, J = 11.3 and 25.4 Hz, 8F, F-ortho); UV–vis (DMSO): kmax
ditriazole derivatives 5b and 5b0, which were separated by preparative TLC.
However, due to the similarity of their NMR spectra, it was not possible to
differentiate these two isomers.
20. Azidoquinolone
4 was obtained from the reaction of the corresponding
quinolone diazonium salt with sodium azide. The experimental details of
this synthesis will be published elsewhere.
21. The synthesis of an azidoquinolone analogous to 4 was recently published
Leyva, S.; Leyva, E. Tetrahedron 2007, 63, 2093–2097.
22. General procedure for the 1,3-dipolar cycloadditions: each of metalloporphyrin
3a–d (0.03 mmol) and the 6-azidoquinolone 4 (2–8 equiv.) were dissolved in
(log
e) = 337 (4.5), 423 (5.3), 553 (3.9) nm; HRMS (ESI) m/z calcd for
C112H76F16N20O16ZnNa2 [M+2Na]2+ 1185.2284, found 1185.2321.