Synthesis and reactions of meso-(p-nitrophenyl)porphyrins

Article abstract of DOI:10.1016/j.tet.2004.01.080

An improved methodology is reported for the regioselective nitration of the phenyl groups of meso-tetraphenylporphyrin 1, using NaNO₂ and TFA. The degree of nitration is easily controlled by the equivalent amount of NaNO₂ used and th

Full text of DOI:10.1016/j.tet.2004.01.080

Tetrahedron 60 (2004) 2757–2763
Synthesis and reactions of meso-(p-nitrophenyl)porphyrins
*
Raymond Luguya, Laurent Jaquinod, Frank R. Fronczek, M. Grac¸a H. Vicente
*
and Kevin M. Smith
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA
Received 20 November 2003; accepted 26 January 2004
Abstract—An improved methodology is reported for the regioselective nitration of the phenyl groups of meso-tetraphenylporphyrin 1, using
NaNO2 and TFA. The degree of nitration is easily controlled by the equivalent amount of NaNO2 used and the reaction time. The
nitroporphyrins are reduced to the corresponding aminoporphyrins under standard SnCl2/HCl conditions. Reaction of tri-aminoporphyrin 9
with 1-formyl-o-carborane followed by reduction using NaBH4 gave a novel tri-carboranylporphyrin bearing amine linkages between the
porphyrin and the carborane groups.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
porphyrin derivatives bearing one, two or three water-
solubilizing groups, such as –NMe3þ, have demonstrated
increased photodynamic efficacy compared with more
hydrophilic, symmetric macrocyles.5,10,11 On the other
hand, nitro-substituted aromatic compounds have been
found to be effective electron-affinity radiosensitizers.12
Therefore, nitro- and amino-substituted amphiphilic por-
phyrins are useful synthetic precursors to biologically active
molecules. Furthermore, nitro and amino groups can be
easily functionalized,11,13,14 and conjugated with bioactive
molecules, such as monoclonal antibodies,15 oligomeric
carboranyl phosphate diesters,16 polymer backbones,17 and
cyclodextrins.18
Porphyrin-type compounds have been actively investigated
as sensitizing drugs for application in cancer diagnosis and
treatment using photodynamic therapy (PDT)1 and also
using boron neutron capture therapy (BNCT).2 PDT and
BNCT are binary therapies that involve activation of a
tumor-localized sensitizer with light (in PDT) or low-energy
neutrons (in BNCT). The main cytotoxic species generated
in PDT is believed to be singlet oxygen, which causes
effective photo-oxidative damage to tumor tissue.3 On the
other hand in BNCT, the high linear energy transfer
4
7
particles He2þ and Li3þ are produced, which cause cell
damage via ionization processes.2,4 In the last decade, two
porphyrin derivatives were approved by the Food and Drug
Administration for the PDT treatment of various conditions
and many other promising derivatives are currently being
evaluated in preclinical and clinical studies.5 From these
investigations it is known that certain porphyrin derivatives
have the ability to selectively localize in tumor tissues,
possibly as a result of their affinity for carrier biomolecules
and/or biological membranes.6 In particular, positively-
charged porphyrins, such as meso-tetra(methylpyridyl)- and
tetra-(trimethylaminophenyl)-porphyrins, have been shown
to strongly interact with the negatively charged groups of
potential biological targets, such as certain proteins,5 DNA7
and RNA,8 and to be effective photosensitizers for PDT.5,9 It
has been shown that the number and distribution of positive
charge about the porphyrin macrocycle plays a very
important role in photodynamic efficacy.5 Amphiphilic
Current synthetic routes to mono-, di- and tri-nitro
functionalized meso-tetraphenylporphyrins involve total
synthesis via a crossed Rothemund approach,17 or by
electrophilic nitration of the p-phenyl groups of meso-
tetraphenylporphyrin (TPP, 1).19,20 In the first method
co-condensation of pyrrole, benzaldehyde and nitrobenz-
aldehyde, results in low to moderate yields of the targeted
porphyrins, which can be tedious to purify from the result-
ing reaction mixtures. Whereas this is the methodology of
choice for the synthesis of o- and m-nitrophenylporphyrins,
higher yields of p-nitrophenylporphyrins can be obtained by
direct nitration of the p-positions of the meso-phenyl groups.
Using fuming nitric acid Kruper et al.19 obtained mono-
nitroporphyrin 2 in moderate yields (46–56%) by direct
nitration of TPP 1 in chloroform solution. Under these
conditions further nitration of 2 gave up to 28% yield of the
di-nitroporphyrins and about 20% of the tri-nitroporphyrin.
Macrocyclic degradation products were also observed.
Higher yields were reported by Meng et al.20 using a
combination of nitric acid and acetic or sulfuric acids
(namely up to 74% yield for mono-nitroporphyrin 2), and
Keywords: Aminoporphyrins; Carboranylporphyrins; Nitration;
Porphyrins; Reductive amination.
*
Corresponding authors. Tel.: þ1-225-578-4422; fax: þ1-225-578-5983;
e-mail address: kmsmith@lsu.edu
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.01.080

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R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
reaction times ranging from 1 h to 7 days. These somewhat
milder reaction conditions produced better yields of the
targeted nitroporphyrins; we rationalized that even milder
conditions should lead to higher yields and regioselectivity
of mono-, di- and tri-nitroporphyrins, with minimum
macrocyclic degradation. These resulting nitroporphyrins
can then be easily reduced to the corresponding amino-
porphyrins and/or further derivatized.19–21
that can be nitrated to give the adj-isomer whereas there is
only one that can be nitrated to produce the opp-isomer. To
obtain the tri-nitrophenylporphyrin 5 as the major product a
large excess of sodium nitrite was used and the reaction time
was increased to 1 h. Longer reaction times resulted in the
formation of the tetra-nitro derivative, which was identified
by comparison with a sample of meso-tetra(4-nitrophenyl)-
porphyrin obtained from the condensation of 4-nitrobenz-
aldehyde with pyrrole.
Due to the poor solubility of the nitro-substituted porphyr-
ins, these were converted into the corresponding aminopor-
phyrins by reduction with tin(II) chloride and HCl in yields
of about 50%, as previously reported in the literature.19–21
The resulting aminoporphyrins 6, 7, 8 and 9 were easily
separated by flash column chromatography on silica gel,
using a gradient elution (dichloromethane/petroleum ether).
The two di-aminoporphyrin regioisomers 7 and 8 were
isolated in a 1:2 ratio and showed similar electronic and
NMR spectra. However, there were characteristic differ-
1
ences in the shifts of the b-hydrogens in their H NMR
spectra and the resonances observed in the 13C NMR, which
allowed us to distinguish between the two regioisomers.
The b-hydrogens of 8 appear as two singlets at 8.92 and
8.81 ppm, whereas those of 7 were two doublets with a
coupling constant J¼4.5 Hz, characteristic of b-H/b-H
proton coupling of highly symmetrical di-substituted
porphyrins. The larger number of signals in the 13C NMR
spectrum of the adj-isomer 8 further confirmed its lower
symmetry compared with the opp-isomer 7. The struc-
tures of mono-aminoporphyrin 6 and di-aminoporphyrins 7
and 8 were further confirmed by X-ray crystallography
(Figs. 1–3). Figure 1 shows one of the three crystallo-
graphically independent, centrosymmetric porphyrin mol-
ecules for 6. For this molecule, the porphyrin N atoms
are symmetry-constrained to be coplanar, and the 24-atom
porphyrin ring system is nearly so, exhibiting mean and
2. Results and discussion
We have developed an alternative route to nitro-substituted
porphyrins via regioselective para-phenyl nitration of TPP
1, using sodium nitrite in TFA.22,23 High yields of nitrated
benzene and substituted benzenes have been reported under
˚
maximum deviations of 0.042 and 0.081(3) A, respectively.
This porphyrin plane forms a dihedral angle of 82.3(1)8 with
the unsubstituted phenyl ring, and a smaller angle, 66.37(4)8
with the phenyl ring carrying the NH2 group. Figure 2 shows
one of the three crystallographically independent, centro-
symmetric porphyrin molecules for 7. For this molecule, the
24-atom porphyrin ring system is slightly less coplanar than
in 6, exhibiting mean and maximum deviations of 0.081 and
þ
these conditions, and both NO2 and N2O3 were proposed
as the electrophiles in these reactions.23 By varying the
amount of sodium nitrite and the reaction time, selective
nitration of one or more of the phenyl groups of TPP can be
achieved, leading to the ready preparation of porphyrins 2,
3, 4 and 5 in high yields. Reduction of the nitro groups with
excess tin(II) chloride gives the corresponding aminopor-
phyrins (6, 7, 8 and 9).
˚
0.168(2) A, respectively. The phenyl rings are twisted out of
the porphyrin plane by about 608, forming dihedral angles of
58.22(6)8 (phenyl) and 63.23(9)8 (aminophenyl) with it. The
structure of porphyrin 8 is shown in Figure 3. Its 24-atom
porphyrin ring system is also nearly planar, exhibiting a
When a concentrated solution of TPP 1 in TFA was treated
with 1.8 equiv. of NaNO2 for 3 min, the mono-nitroporphyrin
2 was obtained as the major product in 80–90% yield.
Increasing the amount of NaNO2 to 8.1 equiv. resulted in the
formation of a mixture of the two isomeric di-nitrophenyl-
porphyrins 3 and 4 as the major products, after only 1.5 min.
Thin layer chromatography (TLC) of the reaction mixture
showed two spots of similar rf in the ratio of about 1:2,
and trace amounts of a more polar fraction, the tri-
nitroporphyrin 5.
˚
˚
mean deviation of 0.055 A and a maximum of 0.131(7) A,
as a result of the internal hydrogen bonds, with N· · ·N
˚
distances of 2.905(7)–2.954(7) A. The phenyl rings are
twisted out of the porphyrin plane by about 608 (torsion
angle magnitudes 58.2(8)–77.0(8)8).
Aminoporphyrins 6, 7, 8 and 9 are readily converted into
amphiphilic water-soluble molecules, for example by
alkylation or by condensation with carboxylic acid-contain-
ing molecules.13–18,24 We recently reported the condensa-
tion of porphyrin 6 with a dimeric carboranyl phosphate
diester via an amide linkage, to give a negatively-charged
conjugate, which is currently being evaluated in our
Based on statistics, the fastest running band was identified
as the opp-isomer 3, and the main second band as the adj-
isomer 4. After mono-nitration, there are two phenyl rings

R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
2759
Figure 1. ORTEP diagram, showing the molecular structure of 6. The molecule packs in the crystal such that there is 50% population of the amino group on the
two diametrically opposed phenyl rings; only one form is shown.
Figure 2. ORTEP diagram showing the molecular structure of 7.

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R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
Figure 3. ORTEP diagram showing the molecular structure of 8.
laboratories as a boron delivery agent for BNCT.16
Alkylation of aminoporphyrins 7 and 8 with methyl iodide
in the presence of a bulky base produced two positively
charged porphyrins, DADP-o and DADP-a, with potential
application in PDT.11 Reductive amination25 of 1-formyl-o-
carborane using tri-aminoporphyrin 9, leads to a tri-
carboranylporphyrin with potential application in BNCT
(Scheme 1).
soluble, amphiphilic porphyrins for application as sensi-
tizers in the PDT and/or the BNCT of cancers. As an
example of their versatility, a tri-aminoporphyrin was
condensed with 1-formyl-o-carborane to produce a tri-
carboranyl-imineporphyrin, which was reduced to the
corresponding amine and converted into a water-soluble
tri-carboranylporphyrin, bearing amine linkages between
the porphyrin and the carborane groups.
Reaction of porphyrin 9 with 1-formyl-o-carborane 1026
produced the imineporphyrin 11, which upon reduction with
sodium borohydride afforded porphyrin 12 in 47% overall
yield. In order to increase the solubility of this porphyrin in
water, the closo-carboranyl cages were degraded to the
corresponding nido-cages using a mixture of pyridine and
piperidine (3:1) as reported previously,27,28 to afford the
negatively-charged water-soluble porphyrin 13. The bio-
logical evaluation of porphyrin 13 is currently underway in
our laboratories.
4. Experimental
4.1. General
Silica gel 60 (70–230 and 230–400 mesh, Merck) or neutral
alumina (Merck; usually Brockmann Grade III) were used
for column chromatography. Analytical thin layer
chromatography (TLC) was performed using Merck 60
F254 silica gel (pre-coated sheets, 0.2 mm thick). Reactions
1
were monitored by TLC and spectrophotometry. H NMR
spectra were obtained in deuterochloroform or acetone-d6
solution, using a Brucker 250 or 400 MHz spectrometer;
chemical shifts are expressed in ppm relative to chloroform
(7.26 ppm) and/or TMS (0 ppm). Unless otherwise stated,
electronic absorption spectra were measured in dichloro-
methane solution using a Hewlett–Packard 8450A spectro-
photometer. Mass spectra were obtained at the Mass
Spectrometry Facility at Louisiana State University, or at
the University of California, San Francisco. Sodium nitrite,
sodium borohydride, tin(II) chloride and trifluoroacetic acid
(TFA) were purchased from Sigma-Aldrich and used
without further purification. Anhydrous sodium sulfate,
3. Conclusions
We have developed a mild method for electrophilic nitration
of the phenyl groups of TPP, by using sodium nitrite in the
presence of TFA. This approach is highly regiospecific
allowing only nitration at the para position of the phenyl
groups in TPP and provides selective control in the number
of phenyl groups nitrated by varying the amount of sodium
nitrite and the duration of the reaction. The nitroporphyrins
are easily reduced to their corresponding aminoporphyrins,
which are valuable intermediates in the synthesis of water-

R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
2761
Scheme 1. Syntheses of tri-carboranylporphyrins 11–13.
sodium bicarbonate and all solvents were purchased from
Fisher Scientific. Dried solvents were obtained according to
literature procedures.29
water before being dried over anhydrous Na2SO4. Recrys-
talization from dichloromethane gave 120 mg (62%) of
porphyrin 5. MS (MALDI) m/z 749.8 (Mþ); 1H NMR
(CDCl3) d ppm: 22.80 (br, 2H), 7.80 (m, 3H), 8.20 (m, 2H),
8.40 (d, J¼7.50 Hz, 6H), 8.65 (d, J¼7.50 Hz, 6H), 8.80 (m,
4.1.1. 5,10,15-Tris(4-nitrophenyl)-20-phenylporphyrin
(5). To a solution of 1 (160 mg, 0.261 mmol) in TFA
(10 mL) was added sodium nitrite (660 mg, 9.57 mmol).
After 55 min stirring at room temperature, the reaction was
quenched with water (100 mL) and the mixture extracted
with dichloromethane (6£25 mL). The organic layers were
washed once with saturated aqueous NaHCO3 and once with
6H), 8.93 (d, J¼5.0 Hz, 2H). UV–Vis (CHCl3) lmax
:
420 nm (1 368,500), 514 (28,400), 549 (14,100), 589 (9800)
and 645 (5600). Anal. Calcd for C44H27N7O6·1.5H2O: C,
68.03; H, 3.89; N, 12.66. Found: C, 67.82; H, 3.71; N, 12.75.
4.1.2. 5-(4-Aminophenyl)-10,15,20-triphenylporphyrin

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R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
(6). To a solution of 1 (100 mg, 0.163 mmol) in TFA
(10 mL) was added sodium nitrite (20 mg, 0.29 mmol).
After 3 min stirring at room temperature, the reaction
mixture was poured into water (100 mL) and extracted with
dichloromethane (6£25 mL). The organic layer was washed
with saturated aqueous NaHCO3 and water as described
above and then the solvent was removed under vacuum. The
residue was purified on a plug of silica gel, eluting with
dichloromethane. After evaporation of the solvent, the
residue was dissolved in concentrated hydrochloric acid
(10 mL) and, while stirring, tin(II) chloride (220 mg,
0.975 mmol) was carefully added. The final mixture was
heated to 65 8C for 1 h under argon before being poured into
cold water (100 mL). The aqueous solution was neutralized
with ammonium hydroxide until pH 8. The aqueous solution
was extracted with dichloromethane until colorless. The
organic layer was then concentrated under vacuum and the
residue was purified on a plug of alumina using dichloro-
methane for elution. The final residue was recrystallized
from methanol, yielding 55.3 mg (54%) of porphyrin 6. The
spectroscopic data obtained for the title compound are in
agreement with those in the literature;19 MS (MALDI) m/z
629.8 (Mþ); 1H NMR (CDCl3) d ppm: 22.75 (br, 2H), 4.02
(s, 2H), 7.07 (d, J¼9.0 Hz, 2H), 7.75 (m, 9H), 7.98 (d,
J¼9.0 Hz, 2H), 8.20 (m, 6H), 8.84 (s, 6H), 8.96 (s, 2H).
UV–Vis (CHCl3) lmax: 417.5 nm (1 315,800), 514
(28,900), 551 (20,600), 589 (15,600) and 645.5 (12,800).
Anal. Calcd for C44H31N5·0.5H20: C, 82.79; H, 4.98; N,
10.98. Found: C, 82.55; H, 5.11; N, 10.95.
4.1.4. 5,10,15-Tris(4-aminophenyl)-20-phenylporphyrin
(9). meso-Tris(4-nitrophenyl)phenylporphyrin 5 (100 mg,
0.163 mmol) was dissolved in hydrochloric acid (40 mL)
and, while stirring, tin(II) chloride (540 mg, 2.39 mmol)
was carefully added. The final mixture was heated to 65 8C
for 1 h under argon before being poured into cold water
(100 mL). The aqueous solution was neutralized with
ammonium hydroxide until pH 8. The aqueous solution
was extracted with dichloromethane until colorless. The
organic layer was then concentrated under vacuum and the
residue purified on a plug of alumina using dichloromethane
for elution. The final residue obtained was recrystallized
from petroleum ether, yielding 47 mg (54%) of the title
compound. MS (MALDI) m/z 658.5 (Mþ); 1H NMR
(CDCl3) d ppm: 22.72 (br, 2H), 4.05 (s, 6H), 7.08 (d,
J¼7.82 Hz, 6H), 7.76 (m, 3H), 7.99 (d, J¼7.82 Hz, 6H),
8.22 (m, 2H), 8.81 (d, J¼4.69 Hz, 2H), 8.92 (m, 6H). UV–
Vis (CHCl3) lmax: 423 nm (1 256,000), 518 (10,400), 558
(9500), 593 (3600) and 652 (4480). Anal. Calcd for
C44H33N7·H2O: C, 78.07; H, 5.70; N, 14.49. Found: C,
78.12; H, 5.20; N, 14.26.
4.1.5. 5,10,15-Tris(4-carboranyliminophenyl)-20-
phenylporphyrin (11). meso-Tris-(4-aminophenyl)phenyl-
porphyrin 9 (50 mg, 0.076 mmol) and 1-formyl-o-carborane
(180 mg, 1.05 mmol) were dissolved in THF (15 mL) at
room temperature under argon. The mixture was heated at
100 8C for 1 h until all the porphyrin was consumed (TLC),
and then poured into water and extracted with dichloro-
methane. The dichloromethane extract was dried over
NaSO4 anhydrous and then concentrated under vacuum.
The residue was purified on alumina column using
dichloromethane for elution. The final residue obtained
was recrystallized from hexane, yielding 40 mg (48%) of the
title product. HRMS (MALDI-QTOF) for C53H63N7B30þH:
calculated m/z 1123.8230, found 1123.8210; 1H NMR
(CDCl3) d ppm: 22.80 (br, 2H), 1.6–3.0 (br, 30H), 4.70
(s, 3H), 7.49 (d, J¼9.3 Hz, 6H), 7.77(m, 3H), 8.18 (m, 5H),
8.22 (d, J¼9.3 Hz, 6H), 8.85(m, 8H). UV–Vis (CHCl3)
4.1.3. 5,15-Bis(4-aminophenyl)-10,20-diphenylporphyrin
(7) and 5,10-bis(4-aminophenyl)-15,20-diphenylpor-
phyrin (8). To a solution of TPP (200 mg, 0.326 mmol)
in TFA (10 mL) was added sodium nitrite (183 mg,
2.65 mmol). After 90 seconds stirring at room temperature,
the reaction was poured into water (100 mL) and extracted
with dichloromethane (6£25 mL). The residue obtained was
purified as described above and then reduced using 0.8 g
(3.55 mmol) of tin(II) chloride and 50 mL of HCl. The two
regioisomers were eluted with dichloromethane (the 5,10-
isomer eluted first) and were recrystallized from methanol,
yielding 52 mg (43%) of the 5,10-isomer and 13 mg (21%)
of the 5,15-isomer. The spectroscopic data obtained for
the title compounds are in agreement with those in the
literature.20 For the opp-isomer 7: MS (MALDI) m/z 644.38
(Mþ), MS (ESI) 645.77 (Mþþ1); 1H NMR1H NMR
(CDCl3) d ppm: 22.74 (br, 2H), 4.04 (s, 4H), 7.06 (d,
J¼9.0 Hz, 4H), 7.74 (m, 6H), 7.99 (d, J¼9.0 Hz, 4H), 8.21
(m, 4H), 8.81 (d, J¼4.5 Hz, 4H), 8.92 (d, J¼4.5 Hz, 4H).
13C NMR (CDCl3) d ppm: 113.7, 122.5, 126.8, 127.8, 134.7,
135.8, 142.5, 146.1. UV–Vis (CHCl3) lmax: 420 nm (1
278,000), 517 (13,500), 555 (9570), 591 (4300) and 649
(4600). Anal. Calcd for C44H32N6·1.5H2O: C, 78.66; H,
5.25; N, 12.52. Found: C, 78.25; H, 5.00; N, 12.22. For the
lmax: 421 (364,000), 516 (17,700), 552 (10,800), 590 (6330)
and 646 (5460).
4.1.6. 5,10,15-Tris[(4-carboranylaminomethyl)phenyl]-
20-phenylporphyrin (12). To a solution of porphyrin 11
(40 mg, 0.036 mmol) in THF (10 mL) was added excess
sodium borohydride (22 mg, 0.582 mmol) and the final
mixture was stirred at room temperature for 1 h, under
argon. Water was slowly added and the final mixture
extracted with dichloromethane (4£20 mL). The dichloro-
methane extracts was dried over NaSO4 anhydrous and
evaporated to dryness. The residue was recrystallized from
dichloromethane and methanol to give 39 mg (98%) of the
title product. HRMS (MALDI-QTOF) for C53H69N7B30þH:
calculated m/z 1129.8700, found 1129.8687; 1H NMR
(CDCl3) d ppm: 22.77 (br, 2H), 1.0–3.0 (br, 30H), 3.96
(s, 3H), 4.12 (d, J¼7.4 Hz, 6H), 4.37 (t, 3H), 6.95 (d,
J¼8 Hz, 6H), 7.74 (m, 3H), 8.01(d, J¼8 Hz, 6H), 8.19
(m, 2H), 8.82 (m, 8H). UV–Vis (CHCl3) lmax: 424 (1
334,000), 519 (16,000), 558 (13,500), 592 (6140) and 651
(7040).
1
adj-isomer 8: MS (MALDI) m/z 644.38 (Mþ); H NMR
(CDCl3) d ppm: 22.74 (br, 2H), 4.03 (s, 4H), 7.06 (d,
J¼8.0 Hz, 4H), 7.76 (m, 6H), 7.99 (d, J¼8.0 Hz, 4H), 8.21
(m, 4H), 8.81 (s, 4H), 8.92 (s, 4H). 13C NMR (CDCl3) d
ppm: 113.7, 120.5, 126.8, 127.8, 132.7, 134.7, 135.9, 142.5,
146.1. UV–Vis (CHCl3) lmax: 420 nm (1 181,100), 517
(14,700), 554 (11,400), 590 (6000) and 647 (5200). Anal.
Calcd for C44H32N6·0.5H2O: C, 80.89; H, 5.02; N, 12.87.
Found: C, 80.73; H, 5.14; N, 12.76.
4.1.7. 5,10,15-Tris[(4-nido-carboranylaminomethyl)
phenyl]-20-phenylporphyrin (13). Porphyrin 12 (20 mg,

R. Luguya et al. / Tetrahedron 60 (2004) 2757–2763
2763
4. Hawthorne, M. F. Angew. Chem. Int. Ed. Engl. 1993, 32,
950–984.
0.018 mmol) was dissolved in pyridine/piperidine 3:1
(3 mL) and allowed to stir at room temperature for 36 h
under argon. After removing the pyridine and piperidine
under vacuum the residue was dissolved in 40% aqueous
acetone and passed slowly through a Dowex 50WX2–100
resin in the potassium form. The porphyrin fraction was
collected, dried under vacuum, redissolved in 70% aqueous
acetone and again passed through the ion-exchange resin.
After removal of the solvent under vacuum the title nido-
carboranylporphyrin 13 was obtained in quantitative yield.
HRMS (MALDI-QTOF) for C53H69N7B27; calculated m/z
5. Vicente, M. G. H. Curr. Med. Chem., Anticancer Agents 2001,
1, 175–194.
6. Osterloh, J.; Vicente, M. G. H. J. Porphyrins Phthalocyanines
2002, 6, 305–324.
7. (a) Marzilli, L. G. New J. Chem. 1990, 14, 409–420. (b)
Pratviel, G.; Bernadou, J.; Meunier, B. Angew. Chem. Int. Ed.
Engl. 1995, 34, 746–769.
8. (a) Bustamante, C.; Gurrieri, S.; Pasternack, R. F.; Purrello,
R.; Rizzarelli, E. Biopolymers 1994, 34, 1099–1104. (b)
Magda, D.; Wright, M.; Crofts, S.; Lin, A.; Sessler, J. L. J. Am.
Chem. Soc. 1997, 119, 6947–6948.
1
365.2787; Found 365.2806. H NMR (acetone-d6) d ppm:
22.40 (br, 5H), 1.6–3.0 (br, 27H), 3.50 (m, 6H), 5.10 (br,
3H), 7.07 (m, 6H), 7.79 (m, 3H), 7.96 (m, 6H), 8.22 (m, 3H),
8.76 (m, 2H), 8.99 (m, 6H). UV–Vis (ethanol) lmax: 427 (1
165,000), 520 (10,000), 567 (13,400) and 658 (6600).
9. (a) Villanueva, A.; Jori, G. Cancer Lett. 1993, 73, 59–64. (b)
Villanueva, J. Photochem. Photobiol. B: Biol. 1994, 23,
49–56.
10. Amor, T. B.; Bortolotto, L.; Jori, G. Photochem. Photobiol.
1998, 68, 314–318.
4.2. Molecular structures
11. Kessel, D.; Luguya, R.; Vicente, M. G. H. Photochem.
Photobiol. 2003, 78, 431–435.
The crystal structures of solvates of 6, 7 and 8 were
determined, using data collected at T¼100 K to ¼25.78 with
Mo K radiation on a Nonius KappaCCD diffractometer.
Compounds 6 and 7 were crystallized as the 2/3 dichloro-
methane solvates, and are essentially isostructural, both
having three independent porphyrin molecules, all lying on
inversion centers. Thus, for monoamino compound 6, all
three molecules have the NH2 group disordered into two
half-populated sites related by inversion. In 7, two of the
three independent molecules have ordered NH2 groups,
while third has its NH2 groups disordered onto the alternate
phenyl groups approximately 60% of the time. For 6,
R¼0.091 for 7049 observed data of 9510 unique data. For 7,
R¼0.065 for 6570 observed data of 9971 unique data. For 8,
the disordered solvent region was modeled as 0.6CH2Cl2,
0.4H2O. R¼0.106 for 3598 observed data of 5698 unique
data. The X-ray crystallographic data for 6, 7 and 8 can be
found in supplementary publications CCDC-229546,
CCDC-223888 and CCDC-220719 respectively, available
from the Cambridge Crystallographic Data Centre.
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Acknowledgements
Support from the National Institutes of Health (EB002064)
is gratefully acknowledged.
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