Chlorosulfonated corrole: A versatile synthon for advanced materials

Article abstract of DOI:10.1142/S1088424610002768

The easily accessible 2,17-bis-chlorosulfonated 5,10,15- trispentafluorophenylcorrole is demonstrated as a highly versatile synthon for the preparation of corroles with functional groups that may be used for advanced applications and materials. Examples presented here are useful for donor-acceptor dyads, water-solubility inducing carbohydrates, chirality-inducing sugars and amino acids, and biotin-avidin technology.

Full text of DOI:10.1142/S1088424610002768

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2010; 14: 911–923
DOI: 10.1142/S1088424610002768
Published at http://www.worldscinet.com/jpp/
Chlorosulfonated corrole: a versatile synthon for advanced
materials
Atif Mahammed and Zeev Gross*
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel
Received 31 August 2010
Accepted 26 October 2010
ABSTRACT: The easily accessible 2,17-bis-chlorosulfonated 5,10,15-trispentafluorophenylcorrole is
demonstrated as a highly versatile synthon for the preparation of corroles with functional groups that
may be used for advanced applications and materials. Examples presented here are useful for donor-
acceptor dyads, water-solubility inducing carbohydrates, chirality-inducing sugars and amino acids, and
biotin-avidin technology.
KEYWORDS: corroles, anthraquinone, phthalimide, donor, acceptor, chirality, pegylation, biotin, avidin.
published [7, 3c]. Another strategy for adding functional
groups to H3(tpfc) uses nucleophilic substitution of the
para-F atoms of its meso-pentafluorophenyl substituents.
INTRODUCTION
The contemporary renaissance in corrole chemis-
try may be traced back to two main synthetic break-
Reported nucleophiles utilized under that strategy are
throughs: (a) facile methodologies to triarylcorroles such
2-pyridyllithium [1a], methoxide [8], and amines [9] and
as H3(tpfc) (Scheme 1) [1] and (b) selective substitution
reactions on the β-pyrrole carbon atoms [2]. The initial
1999 discoveries of one-pot syntheses were instrumental
the same approach may also be used for the introduction
of sulfur atoms [10].
We now report the versatile reactions that may be per-
for the current situation: almost any corrole can nowa-
formed on corrole 1-Cl, which serves to demonstrate its
days be prepared by relatively straightforward method-
high value as a synthon for derivatives that may be used
ologies in reasonable yields and quantities [3]. The first
for advanced applications.
reportedfunctionalizationoftriarylcorrolesproceedswith
quite fascinating selectivity: the bis-chlorosulfonated
derivative 1-Cl (Scheme 1) was obtained in 96% purity
(together with 4% of the 3,17-isomer) under conditions
where 139 products could have been formed [4a]. The
main utilization of 1-Cl remains hydrolysis to the bipo-
lar water-soluble corrole 1 with two sulfonic acid head
groups: the corresponding gallium(III), manganese(III),
and iron(III) complexes are of tremendous applicabil-
ity in medicine- and energy-oriented research [5]. Many
other reactions on corrole’s β-pyrroles have been reported
since, but none of them is as selective and most require
metalation prior to functionalization [6]. Fortunately,
several procedures for demetalation have recently been
EXPERIMENTAL
Physical methods
1H and 19F NMR spectra were recorded on a Bruker
Avance 300 spectrometer, operating at 300 M Hz for
1H and 282 M Hz for 19F NMR. Chemical shifts in the
1H NMR spectra are reported in ppm relative to resid-
ual hydrogens in the deuterated solvents, and relative to
CFCl3 (δ = 0.00) in the 19F NMR spectra. Mass spectros-
copy was obtained on a Waters MALDI-TOF instrument,
or by LCT Premier from Waters under ESI condition for
mass direct probe in positive and negative modes, with
solvent acetonitrile:water (70:30), or by TSQ-70B instru-
ment (Finnigan Mat) by desorption chemical ionization
(DCI) and by fast-atom bombardment (FAB) in glycerol
matrices. UV-vis spectral measurements were carried out
SPP full member in good standing
SPP full student member
*Correspondence to: Zeev Gross, email: chr10zg@tx.technion.ac.il
Copyright © 2010 World Scientific Publishing Company

912
A. MAhAMMeD AnD Z. GrOSS
C6F5
C6F5
C6F5
HN
HN
NH HN
HN
NH HN
N
N
hydrolysis
N
HSO3Cl
C6F5
C6F5
C6F5
C6F5
C6F5
C6F5
NH HN
SO2Cl
SO3H
SO2Cl
1-Cl
(96% from H3(tpfc))
SO3H
1
H3(tpfc)
(71% from H3(tpfc))
amidation by piperidine
metalation
(Ph)3P
C6F5
C6F5
C6F5
cobalt
metalation
HN
NH HN
N
N
N
N
N
N
C6F5
M
C6F5
SO3H
C6F5
C6F5
C6F5
Co
C6F5
N
N
N
SO2
N
SO2
N
SO2
SO3H
SO2
N
N
M (% yield from 1) = FeIII (95),
GaIII (90), MnIII (94), AlIII(82),
CuIII (96), RhIII (85), CoIII (90),
SnIV (92), SbV (84)
2-Co
(71% from H3(tpfc))
2
(100% from 1-Cl)
Scheme 1. Preparation of corrole 1-Cl and previously reported reactions performed on it
with HP8453 Diode Array Spectrophotometer. Circular
Dichroism (CD) spectra were recorded on JASCO J-810
Spectropolarimeter.
Hz, 1F), -165.6 (m, 2F), -166.2 (m, 2F), -168.0 (m, 2F).
UV-vis (MeOH): λmax, nm (ε, M-1.cm-1) 418 (90,000), 638
(42,000). MS (MALDI negative): m/z 1039.0 [M - H]-.
Synthesis of 4. 50 mg of 3 (0.05 mmol) were dissolved
in 20 mL pyridine and 200 mg of phthalic anhydride
(1.35 mmol) was added under nitrogen. The solution was
stirred for 1 h at rt and heated under reflux for another
24 h, followed by solvent evaporation. Column chroma-
tography on silica gel 60 (eluent: CH2Cl2, then CH2Cl2/
EtOAc 1:1) afforded 4 as a dark purple solid (yield: 43
mg, 69%). 1H NMR (CD3OD): δ, ppm 9.29 (s, 1H), 8.49
Materials
Corroles H3(tpfc), 1-Cl and 1 were prepared accord-
ing to the published procedures [2, 4]. All solvents and
reagents were of high purity grades and purchased from
Sigma-Aldrich.
Synthesis
3
3
(s, 1H), 8.48 (d, JHH = 5.0 Hz, 1H), 8.29 (d, JHH = 5.0
Hz, 1H), 8.23 (d, 3JHH = 5.0 Hz, 1H), 8.21 (d, 3JHH = 5.0
Hz, 1H), 7.50–7.70 (m, 8H, phthalimide), 4.26 (m, 2H),
4.03 (m, 2H), 3.78 (m, 2H), 3.64 (m, 2H). 19F NMR
Synthesis of 3. 90 mg of 1-Cl (0.09 mmol) were dis-
solved in 10 mL CH2Cl2 and titrated during 5 min to a
stirred solution of 60 mL CH2Cl2 that contained 2 mL
ethylenediamine (30 mmol). The solution was stirred for
30 min then washed twice with 0.2 M Na2CO3 and twice
with water. The organic phase was dried by Na2SO4, and
the solvent was evaporated. Column chromatography on
silica gel 60 (eluent: CH2Cl2, followed by CH2Cl2/EtOH
1:1, and finalized with EtOH) afforded 3 as a dark purple
3
4
(CD3OD): δ, ppm -139.4 (dd, JFF = 24.6 Hz, JFF = 6.2
3
4
Hz, 2F), -139.7 (dd, JFF = 22.9 Hz, JFF = 7.0 Hz, 2F),
3
4
-140.9 (dd, JFF = 24.7 Hz, JFF = 6.2 Hz, 2F), -158.0
(t, 3JFF = 19.4 Hz, 1F), -158.7 (t, 3JFF = 21.2 Hz, 1F), -159.5
3
(t, JFF = 22.0 Hz, 1F), -166.1 (m, 2F), -166.6 (m, 4F).
UV-vis (MeOH): λmax, nm (ε, M-1.cm-1) 220 (108,000),
422 (95,000), 642 (43,000). MS (MALDI negative): m/z
1299.0 [M - H]-.
1
solid (yield: 70 mg, 74%). H NMR (CD3OD): δ, ppm
3
9.60 (s, 1H), 8.60 (s, 1H), 8.43 (d, JHH = 5.1 Hz, 1H),
8.25 (d, 3JHH = 5.1 Hz, 1H), 8.17 (d, 3JHH = 5.1 Hz, 1H),
Synthesis of 4-Ga. 20 mg of 4 (0.015 mmol) were
dissolved in 10 mL pyridine and 100 mg of anhydrous
GaCl3 (0.57 mmol) was added under nitrogen. The solu-
tion was heated to reflux for 15 min, after which the sol-
vent was evaporated. Column chromatography on silica
gel 60 (eluent: CH2Cl2/EtOAc 1:1, then CH2Cl2/EtOAc
3
8.14 (d, JHH = 5.1 Hz, 1H), 3.33 (6.0 Hz, t, 2H), 3.14
(6.0 Hz, t, 2H), 2.77 (6.0 Hz, t, 2H), 2.62 (6.0 Hz, t, 2H).
3
19F NMR (CD3OD): δ, ppm -139.0 (dd, JFF = 24.1 Hz,
4JFF = 7.7 Hz, 2F), -140.2 (m, 4F), -157.3 (t, 3JFF = 20.0 Hz,
3
3
1F), -158.2 (t, JFF = 20.0 Hz, 1F), -159.2 (t, JFF = 20.0
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 912–923

ChlOrOSulfOnAteD COrrOle: A verSAtIle SynthOn fOr ADvAnCeD MAterIAlS
913
1:2) afforded 4-Ga as a dark purple solid (yield: 19 mg,
ammonia solution (7N in methanol). The vial was closed
and stirred in the dark at rt for 2 days, followed by sol-
vent evaporation. Column chromatography on silica gel
60 (eluent: CH2Cl2/EtOH 4:1, then CH2Cl2/EtOH 1:1)
afforded 7 as a dark purple solid (yield: 45 mg, 95%). 1H
NMR (CD3OD): δ, ppm 10.08 (s, 1H), 8.67 (s, 1H), 8.46
(d, 3JHH = 4.8 Hz, 1H), 8.32 (d, 3JHH = 4.8 Hz, 1H), 8.22
(d, 3JHH = 4.8 Hz, 1H), 8.19 (d, 3JHH = 4.8 Hz, 1H), 5.44 (d,
3JHH = 3.1 Hz, 1H), 3.2-4.2 (m, 13H). 19F NMR (CD3OD):
1
86%). H NMR (CD3OD): δ, ppm 9.48 (s, 1H), 8.87 (d,
3JHH = 4.8 Hz, 1H), 8.82 (s, 1H), 8.70 (d, 3JHH = 4.8 Hz,
1H), 8.61 (d, 3JHH = 4.8 Hz, 1H), 8.60 (d, 3JHH = 4.8 Hz,
1H), 8.00 (1H, p-pyridine), 7.60-7.80 (m, 8H, phthalim-
ide), 8.00 (br s, 1H, o-pyridine), 7.30 (dd, 7.7 Hz, 5.6 Hz,
2H, m-pyridine), 5.42 (dd, 5.6 Hz, 2.2 Hz, 2H, o-pyri-
dine), 4.00 (m, 2H), 3.86 (m, 2H), 3.58 (m, 2H), 3.38 (m,
2H). 19F NMR (CD3OD): δ, ppm -139.4 (dd, 3JFF = 24.2
Hz, 4JFF = 6.3 Hz, 2F), -140.0 (dd, 3JFF = 22.4 Hz, 4JFF
=
δ, ppm -135.1 (d, JFF = 22.0 Hz, 2F), -136.5 (m, 4F),
3
7.3 Hz, 2F), -141.2 (dd, 3JFF = 24.1 Hz, 4JFF = 6.8 Hz, 2F),
-153.8 (t, JFF = 20.0 Hz, 1F), -154.8 (t, JFF = 20.0 Hz,
1F), -156.1 (t, 3JFF = 20.0 Hz, 1F), -162.0 (m, 2F), -162.8
(m, 2F), -164.5 (m, 1F), -164.9 (m, 1F). UV-vis (MeOH):
3
3
3
3
-156.6 (t, JFF = 20.0 Hz, 1F), -157.1 (t, JFF = 20.2 Hz,
1F), -158.2 (t, 3JFF = 22.0 Hz, 1F), -165.3 (m, 2F), -165.5
(m, 2F), -165.6 (m, 2F). UV-vis (MeOH): λmax, nm (ε,
M-1.cm-1) 218 (107,000), 426 (140,000), 596 (41,000),
620 (50,000). MS (MALDI negative): m/z 1366.0
[M - pyridine]-.
λ
max, nm (ε, M-1.cm-1) 420 (55,000), 440 (45,000), 636
(24,000). UV-vis (buffer solution, pH 7.0): λmax, nm (ε,
M-1.cm-1) 414 (42,000), 433 (31,000), 631 (17,000). MS
(MALDI positive): m/z 1301.4 [M + Na]+.
Synthesis of 5. 40 mg of 1-Cl (0.04 mmol) were
dissolved in 200 mL CH2Cl2 and 200 mg of 1-amino-
anthraquinone (0.9 mmol) was added. The solution was
stirred for 3 h, after which the solvent was evaporated.
Column chromatography on silica gel 60 (eluent: CH2Cl2,
then CH2Cl2/EtOAc 2:1) afforded 5 as a dark green solid
(yield: 42 mg, 76%). 1H NMR (CD3OD): δ, ppm 9.29 (s,
1H), 8.19 (3H, β-pyrrole), 8.00-8.10 (m, 2H β-pyrrole +
1H anthraquinone (AQ)), 7.90-8.00 (m, 3H, AQ), 7.30-
7.70 (m, 6H, AQ), 6.84 (d, 3JHH = 7.5 Hz, 1H, AQ), 6.45
Synthesis of 6-Ga. 40 mg of 6 (0.025 mmol) were dis-
solved in 10 mL pyridine and 100 mg of anhydrous GaCl3
(0.57 mmol) was added under nitrogen. The solution was
heated to reflux for 15 min, followed by solvent evapora-
tion. Column chromatography on silica gel 60 (eluent:
CH2Cl2/CH3CN3:1) afforded 4-Ga as a dark purple solid
1
(yield: 35 mg, 84%). H NMR (CD3OD): δ, ppm 9.64
3
(s, 1H), 8.80 (s, 1H), 8.78 (d, JHH = 4.8 Hz, 1H), 8.62
3
3
(d, JHH = 4.8 Hz, 1H), 8.53 (t, JHH = 4.8 Hz, 2H), 5.98
(d, 3JHH = 8.7 Hz, 1H), 5.80 (d, 3JHH = 8.7 Hz, 1H), 5.45
(t, 3JHH = 9.8 Hz,1H), 5.32 (t, 3JHH = 9.8 Hz,1H), 5.11 (t,
3
(t, JHH = 7.2 Hz, 1H, AQ), 5.94 (m, 2H, AQ). 19F NMR
3
4
3
(CD3OD): δ, ppm -138.7 (dd, JFF = 24.7 Hz, JFF = 4.2
3JHH = 9.8 Hz, 1H), 5.07 (t, JHH = 9.8 Hz, 1H), 3.8-4.4
3
4
Hz, 2F), -140.3 (dd, JFF = 23.6 Hz, JFF = 7.1 Hz, 2F),
-140.5 (dd, JFF = 21.6 Hz, JFF = 5.1 Hz, 2F), -157.3
(t, JFF = 17.6 Hz, 1F), -158.4 (t, JFF = 21.1 Hz, 1F),
-158.5 (t, JFF = 21.1 Hz, 1F), -165.7 (m, 2F), -166.4
(m, 8H), 2.04 (s, 6H), 1.97 (s, 3H), 1.93 (s, 3H), 1.73 (s,
3
4
3H), 1.49 (s, 3H), 1.42 (s, 3H), 1.28 (s, 3H). 19F NMR
3
3
3
(CD3OD): δ, ppm -135.0 (d, JFF = 23.0 Hz, 1F), -135.4
3
3
3
(d, JFF = 23.0 Hz, 1F), -136.4 (d, JFF = 23.0 Hz, 2F),
3
3
(m, 2F), -166.9 (m, 2F). UV-vis (MeOH): λmax, nm (ε,
M-1.cm-1) 256 (62,000), 418 (76,000), 650 (33,000). MS
(MALDI negative): m/z 1365.0 [M - H]-.
-136.9 (d, JFF = 23.0 Hz, 2F), -152.7 (t, JFF = 20.0 Hz,
1F), -153.5 (t, 3JFF = 20.0 Hz, 1F), -155.1 (t, 3JFF = 20.0 Hz,
1F), -161.3 (m, 2F), -161.8 (m, 2F), -163.9 (m, 2F). MS
(MALDI negative): m/z 1716.2 [(M - H) + Cl]-.
Synthesis of 6. 150 mg of 1-Cl (0.15 mmol) were
dissolved in 20 mL CH2Cl2 and 200 mg (0.58 mmol) of
2-aminotetra-O-acetyl-2-deoxy-β-D-glucose [11] was
added. The solution was stirred for 24 h and then evapo-
rated. Column chromatography on silica gel 60 (eluent:
CH2Cl2, then CH2Cl2/CH3CH 4:1, then CH2Cl2/CH3CH
3:2) afforded 6 as a green solid (yield: 113 mg, 46%). 1H
NMR (CD3OD): δ, ppm 9.58 (s, 1H), 8.63 (s, 1H), 8.46
(d, 3JHH = 4.8 Hz, 1H), 8.25 (d, 3JHH = 4.8 Hz, 1H), 8.20
(d, 3JHH = 4.8 Hz, 1H), 8.18 (d, 3JHH = 4.8 Hz, 1H), 5.60
Synthesis of 7-Ga. 10 mg of 6-Ga (0.006 mmol) were
dissolved into small vial that contained 8 mL methanol/
H2O/triethylamine (2:1:1). The vial was closed and stirred
in the dark at rt for 2 days, followed by solvent evapora-
tion. Column chromatography on silica gel 60 (eluent:
CH2Cl2/EtOH4:1, then CH2Cl2/EtOH1:1) afforded 7-Ga
as a dark green (yield: 6 mg, 75%). 1H NMR (CD3OD):
3
δ, ppm 10.35 (s, 1H), 8.90 (s, 1H), 8.78 (d, JHH = 4.8
Hz, 1H), 8.66 (d, 3JHH = 4.8 Hz, 1H), 8.52 (d, 3JHH = 4.8
3
3
(d, JHH = 8.6 Hz, 2H), 5.30 (m, 4H), 3.8-4.3 (m, 8H),
Hz, 2H), 5.54 (d, JHH = 3.1 Hz, 1H), 3.3-4.2 (m, 13H).
1.98 (s, 6H), 1.97 (s, 3H), 1.89 (s, 3H), 1.43 (s, 3H), 1.18
(s, 3H), 0.58 (s, 3H), 0.50 (s, 3H). 19F NMR (CD3OD): δ,
ppm -134.9 (dd, 3JFF = 24.0 Hz, 4JFF = 7.0 Hz, 1F), -135.7
19F NMR (CD3OD): δ, ppm -137.3 (m, 2F), -139.1 (m,
4F), -155.3 (br peak, 1F), -156.1 (br s, 1F), -157.6 (br
s, 1F), -163.9 (m, 2F), -164.4 (m, 2F), -166.7 (m, 2F).
UV-vis (MeOH): λmax, nm (ε, M-1.cm-1) 427 (68,500),
593 (18,300), 617 (22,000). MS (MALDI negative with
matrix α-cyano-4-hydroxycynamic acid): m/z 1534.6
[M + α-cyano-4-hydroxycynamate]-.
3
4
(dd, JFF = 24.0 Hz, JFF = 7.0 Hz, 1F), -136.4 (m, 4F),
3
3
-153.7 (t, JFF = 20.0 Hz, 1F), -154.8 (t, JFF = 20.0 Hz,
1F), -155.9 (t, 3JFF = 20.0 Hz, 1F), -161.9 (m, 2F), -162.8
(m, 2F), -163.8 (m, 1F), -164.1 (m, 1F). MS (MALDI
positive): m/z 1652.5 [M + K]+.
Synthesis of 7-Co. 20 mg of 7 (0.016 mmol) were
dissolved into 12 mL ethanol. 40 mg of Co(OAc)2·4H2O
(0.16 mmol) were added and the solution was stirred at
Synthesis of 7. 60 mg of 6 (0.037 mmol) were dis-
solved into a small vial that contained 5 mL of an
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 913–923

914
A. MAhAMMeD AnD Z. GrOSS
rt for 1 h. The solvent was evaporated. Column chro-
matography on silica gel 60 (eluent: CH2Cl2/EtOH 2:1)
afforded 7-Co as a brown solid (yield: 18 mg, 86%). 1H
NMR (CD3OD): δ, ppm 10.45 (s, 1H), 8.97 (d, 3JHH = 4.8
Hz, 1H), 8.86 (d, 3JHH = 4.8 Hz, 1H), 8.64 (d, 3JHH = 4.8
Hz, 1H), 8.54 (d, 3JHH = 4.8 Hz, 1H), 8.50 (s, 1H), 5.57 (d,
3JHH = 3.0 Hz, 1H), 3.3-4.0 (m, 13H). 19F NMR (CD3OD):
δ, ppm -137.2 (br s, 2F), -138.6 (br s, 2F), -139.1 (br s,
2F), -155.8 (br s, 1F), -156.5 (br s, 1F), -158.0 (br s, 1F),
-164.2 (br m, 2F), -164.7 (br m, 2F), -166.8 (br m, 1F),
-167.1 (br m, 1F). UV-vis (MeOH): λmax, nm (ε, M-1.cm-1)
430 (34,000), 598 (19,000), 615 (21,500). MS (MALDI
negative): m/z 1334.2 [M]-.
Synthesis of 8. 200 mg of 1-Cl (0.2 mmol) were dis-
solved in 400 mL CH2Cl2. 0.21 mL of tris(2-aminoethyl)
amine (1.4 mmol) were dissolved in 5 mL CH2Cl2 and
titrated to the solution of 1-Cl during 5 min. The solu-
tion was stirred for 24 h at rt. The solvent was evapo-
rated. Column chromatography on silica gel 60 (eluent:
CH2Cl2, then CH2Cl2/CH3CN 2:1, then CH2Cl2/CH3CN
1:3) afforded 5 as a green solid (yield: 40 mg, 19%). 1H
NMR (CD3OD): δ, ppm 9.66 (s, 1H), 8.61 (s, 1H), 8.47
(d, 3JHH = 4.8 Hz, 1H), 8.41 (d, 3JHH = 4.8 Hz, 1H), 8.21
(d, 3JHH = 4.8 Hz, 1H), 8.16 (d, 3JHH = 4.8 Hz, 1H), 3.11
(0.122 mmol) was added and the solution was refluxed
for 2 h. The solvent was evaporated. Column chroma-
tography on silica gel 60 (eluent: CH2Cl2/CH3CN 1:2)
afforded 9-Mn as a dark green solid (yield: 8 mg, 77%).
19F NMR (CD3OD): δ, ppm -125.0 to -135.0 (br s, 6F),
-153.0 (br s, 2F), -155.0 (br s, 1F), -160.0 (br s, 4F),
-162.0 (br s, 2F). UV-vis (CH2Cl2): λmax, nm 425 (Soret),
418 (Soret), 580 (Q-band), 614 (Q-band), 650 (Q-band).
MS (MALDI positive): m/z 1345.4 [M + H]+.
Synthesis of 9-Fe. 10 mg of 9 (0.008 mmol) were dis-
solved in 8 mL pyridine. The solvent was heated until
reflux and under nitrogen atmosphere. 30 mg of FeCl2
(0.24 mmol) was added and the solution was refluxed for
30 min. The solvent was evaporated. Column chroma-
tography on silica gel 60 (eluent: CH3CN/pyridine100:1)
afforded 9-Fe as a brown solid (yield: 8 mg, 77%). 19F
NMR (CD3OD): δ, ppm -114.0 (br s, 2F), -120.0 (br s,
4F), -150.0 (br s, 2F), -153.0 (br s, 1F), -157.0 (br s, 4F),
-160.0 (br s, 2F). UV-vis (CH2Cl2): λmax, nm 405 (Soret),
550 (Q-band). MS (MALDI negative): m/z 1345.4 [M]-.
Synthesis of 10. 70 mg of 1-Cl (0.07 mmol) were dis-
solved in 20 mL CH2Cl2. 200 mg of glycine ethyl ester
(2 mmol) were added and the solution was stirred for 1
h. The solution was washed twice with a solution of HCl
(2 M) and then with distilled water. The solvent was
evaporated and 10 obtained in quantitative yield as a dark
green solid. 1H NMR (CDCl3): δ, ppm 9.48 (s, 1H), 8.44
(s, 1H), 8.29 (d, 3JHH = 4.7 Hz, 1H), 8.11 (d, 3JHH = 4.7 Hz,
1H), 8.01 (d, 3JHH = 4.7 Hz, 2H), 3.74 (q, 3JHH = 7.1 Hz,
(m, 4H), 2.69 (m, 2H), 2.28 (m, 2H), 2.21 (m, 2H), 2.12
3
(m, 2H). 19F NMR (CD3OD): δ, ppm -139.7 (dd, JFF
=
4
24.0 Hz, JFF = 6.0 Hz, 2F), -140.6 (m, 4F), -157.9 (t,
3JFF = 19.0 Hz, 1F), -158.5 (t, 3JFF = 19.0 Hz, 1F), -159.8
3
(t, JFF = 19.0 Hz, 1F), -165.9 (m, 2F), -166.6 (m, 2F),
3
-168.4 (m, 2F). UV-vis (CH3CN): λmax, nm 418 (Soret),
439 (Soret), 698 (Q-band), 633 (Q-band). MS (MALDI
negative): m/z 1064.9 [M - H]-.
4H), 3.45 (s, 4H), 0.87 (t, JHH = 7.1 Hz, 6H). 19F NMR
3
(CDCl3): δ, ppm -138.0 (m, 6F), -153.9 (t, JFF = 21.0
3
3
Hz, 1F), -154.7 (t, JFF = 21.0 Hz, 1F), -155.5 (t, JFF
=
Synthesis of 9. 30 mg of 8 (0.028 mmol) were dis-
solved in 8 mL CH3CN and stirred under nitrogen atmo-
sphere. 20 mg of (+)-biotin (0.27 mmol) were added,
then 20 mg of 2-chloro-4,6-dimethoxy-1,3,5-titrazine
(0.11 mmol). Finally, 30 µl of 4-methylmorpholine (0.27
mmol) were added and the solution was heated until
reflux for 2.5 h. The solvent was evaporated. Column
chromatography on silica gel 60 (eluent: CH2Cl2, then
CH2Cl2/CH3CN 1:2, then CH3CN) afforded 9 as a green
21.0 Hz, 1F), -162.5 (m, 2F), -163.1 (m, 2F), -165.0 (m,
2F). MS (MALDI positive): m/z 1149.2 [M+ Na]+.
Synthesis of 11. 50 mg of 10 (0.05 mmol) added to
100 mL solution of 0.02 M sodium carbonate. The solu-
tion was refluxed for 1 h, after which the basic solution
was neutralized by HCl and washed with CH2Cl2. The
product transferred to the organic phase. The CH2Cl2
washed twice with water and dried by sodium sulfate. 40
mg of 11 were obtained as a dark purple solid (84% yield)
after filtration and evaporation of the CH2Cl2 solution. 1H
NMR (CD3OD): δ, ppm 9.39 (s, 1H), 8.82 (s, 1H), 8.60
(d, 3JHH = 4.8 Hz, 2H), 8.47 (d, 3JHH = 4.8 Hz, 1H), 8.35
1
solid (yield: 22 mg, 60%). H NMR (CD3OD): δ, ppm
3
9.69 (s, 1H), 8.70 (s, 1H), 8.48 (d, JHH = 4.8 Hz, 1H),
8.34 (d, 3JHH = 4.8 Hz, 1H), 8.23 (d, 3JHH = 4.8 Hz, 1H),
8.20 (d, 3JHH = 4.8 Hz, 1H), 4.95 (m, 1H), 4.80 (m, 1H),
3.44 (m,2H), 3.27 (m, 2H), 2.42 (m, 8H), 1.93 (m, 1H),
1.68 (t, 3JHH = 7.5 Hz, 2H), 1.58 (d, 3JHH = 12.6 Hz, 1H),
0.82-1.00 (m, 3H), 0.52 (m, 1H), 0.27 (m, 2H), 0.15 (m,
3
(d, JHH = 4.8 Hz, 1H), 4.03 (s, 2H), 3.72 (s, 2H). 19F
NMR (CD3OD): δ, ppm -140.9 (m, 6F), -155.9 (t, 3JFF
=
20.0 Hz, 1F), -156.5 (t, 3JFF = 20.0 Hz, 1F), -157.2 (t, 3JFF
= 20.0 Hz, 1F), -165.0 (m, 2F), -165.4 (m, 2F), -166.9
(m, 2F). UV-vis (buffer solution, pH 7.0): λmax, nm (ε,
M-1.cm-1) 414 (70,000), 433 (57,000), 630 (28,000). MS
(MALDI positive): m/z 1109.1 [M + K]+.
1H). 19F NMR (CD3OD): δ, ppm -139.3 (dd, 3JFF = 23.0
3
Hz, 4JFF = 8.0 Hz, 2F), -140.2 (dd, JFF = 23.0 Hz, 4JFF
=
8.0 Hz, 4F), -157.6 (t, 3JFF = 19.0 Hz, 1F), -158.6 (t, 3JFF
= 19.0 Hz, 1F), -159.8 (t, 3JFF = 19.0 Hz, 1F), -165.9 (m,
2F), -166.5 (m, 2F), -168.4 (m, 2F). UV-vis (DMSO):
Synthesisof10-Fe. OneportionofFeCl2·4H2O(70mg,
0.35 mmol) was added at once to pyridine solution
(10 mL) of 10 (70 mg, 0.06 mmol), and the mixture was
heated immediately to reflux for 10 min. The product
was purified by silica gel column (the eluent was CH2Cl2/
n-hexane 1:1 at the beginning then CH2Cl2/THF 100:1),
λ
max, nm (ε, M-1.cm-1) 421 (112,000), 442 (91,000), 639
(48,500). MS (MALDI negative): m/z 1291.2 [M - H]-.
Synthesis of 9-Mn. 10 mg of 9 (0.008 mmol) were
dissolved in 10 mL DMF. 30 mg of Mn(OAc)2·4H2O
Copyright © 2010 World Scientific Publishing Company
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ChlOrOSulfOnAteD COrrOle: A verSAtIle SynthOn fOr ADvAnCeD MAterIAlS
915
affording 60 mg (82% yield) of 10-Fe as a brown solid.
(0.57 mmol) was added under nitrogen and the solution
was refluxed for 30 min. The solvent was evaporated.
PTL on silica (eluent: CH2Cl2/EtOH 50:1) afforded
19F NMR (CD3OD): δ, ppm -118.1 (2F), -123.0 (2F),
-124.9 (2F), -153.7 (2F), -156.1 (1F), -160.9 (2F), -161.2
(2F), -163.2 (2F). MS (MALDI negative) m/z (%) 1179.2
(80%) [M]-, 1202.2 (100%) [M + Na]-.
1
13-Ga as a dark purple solid (yield: 18 mg, 87%). H
NMR (CD3OD): δ, ppm 9.45 (s, 1H), 8.82 (s, 1H), 8.70
Synthesis of 11-Fe. 60 mg of 10-Fe (0.05 mmol) and
100 mL solution of 0.05 M sodium carbonate was refluxed
for 1 h, after which the basic solution was neutralized by
HCl and washed with CH2Cl2. The product transferred
to the organic phase. The CH2Cl2 washed twice with
water and dried by sodium sulfate. 45 mg of 11-Fe were
obtained as a brown solid (79% yield) after filtration and
evaporation of the CH2Cl2 solution. 19F NMR (CD3OD):
δ, ppm -118.2 (2F), -123.1 (2F), -125.0 (2F), -153.8 (2F),
-156.1 (1F), -161.1 (4F), -163.3 (2F). MS (MALDI nega-
tive) m/z: 1122.5 [M]-.
(d, 3JHH = 4.6 Hz, 1H), 8.58 (d, 3JHH = 4.6 Hz, 1H), 8.44
3
(d, JHH = 4.6 Hz, 2H), 3.00-3.90 (m, 60H). 19F NMR
3
(CD3OD): δ, ppm -135.0 (d, JFF = 17.0 Hz, 2F), -136.7
3
3
(m, 4F), -153.8 (t, JFF = 20.0 Hz, 1F), -154.7 (t, JFF
=
3
20.0 Hz, 1F), -155.8 (t, JFF = 20.0 Hz, 1F), -161.8 (m,
2F), -162.6 (m, 2F), -164.6 (m, 2F). UV-vis (MeOH):
λ
max, nm (ε, M-1.cm-1) 430 (140,000), 616 (54,000). MS
(MALDI positive): m/z 1629.2 [M + Na]+.
Synthesis of 13-Mn. 20 mg of 13 (0.013 mmol) were
dissolved in 10 mL DMF. 50 mg of Mn(OAc)2·4H2O
(0.2 mmol) was added and the solution was refluxed for
1.5 h. The solvent was evaporated. PTL on silica (elu-
ent: CH2Cl2/EtOH 50:1) afforded 13-Mn as dark green
solid (yield: 17 mg, 82%).%). 19F NMR (CD3OD): δ,
ppm -128.0 to -137.0 (br s, 6F), -152.6 (br s, 2F), -154.7
(br s, 1F), -162.2 (br s, 2F), -163.1 (br s, 2F), -164.2
(br s, 2F). UV-vis (MeOH): λmax, nm (ε, M-1.cm-1) 424
(35,000), 480 (30,000), 536 (8,000), 578 (16,000), 614
(17,000), 648 (25,000). MS (MALDI negative): m/z
1589.4 [M - H]-.
Synthesis of 12. 40 mg of 1-Cl (0.04 mmol) were
dissolved in 50 mL CH2Cl2. 150 mg of L-cysteine ethyl
ester (1 mmol) were added and the solution was stirred
for 1 h. The solution was washed twice with a solution
of HCl (2 M) and then with distilled water. The solvent
was evaporated and 12 obtained in quantitative yield
as a dark purple solid. 1H NMR (CD3OD): δ, ppm 9.35
3
(s, 1H), 8.78 (s, 1H), 8.56 (d, JHH = 4.6 Hz, 1H), 8.54
(d, 3JHH = 4.6 Hz, 1H), 8.44 (d, 3JHH = 4.6 Hz, 1H), 8.28
(d, 3JHH = 4.6 Hz, 1H), 6.40 (d, 3JHH = 8.0 Hz, 1H), 5.96
(d, 3JHH = 8.0 Hz, 1H), 4.51 (m, 2H), 3.94 (m, 2H), 3.55
(m, 2H), 2.94 (d, 3JHH = 6.9 Hz, 4H), 1.48 (t, 3JHH = 8.0 Hz,
Substitution of the para-F atoms of H3(tpfc) by
sulfur atoms, leading to tris-5,10,15-(2′,3′,5′,6′-tetra-
fluoro-4′-thioanisyl)corrole. 100 mg of H3(tpfc) (0.125
mmol) were dissolved in 20 mL DMF. 200 mg of NaHS
(3.6 mmol) was added and the solution was refluxed for
30 min under N2. The solvent was evaporated and the
3
3
1H), 1.40 (t, JHH = 8.0 Hz, 1H), 1.07 (t, JHH = 6.4 Hz,
3
3H), 0.75 (t, JHH = 6.4 Hz, 3H). 19F NMR (CD3OD):
3
3
δ, ppm -137.6 (d, JFF = 23.0 Hz, 2F), -138.3 (d, JFF
=
3
1
23.0 Hz, 2F), -138.8 (d, JFF = 23.0 Hz, 2F), -150.8 (t,
3JFF = 22.3 Hz, 1F), -151.1 (t, 3JFF = 23.3 Hz, 2F), -160.8
(m, 4F), -162.3 (m, 2F). UV-vis (CH2Cl2): λmax, nm 424
(Soret), 596 (Q-band), 580 (Q-band), 640 (Q-band). MS
(ESI negative): m/z 1218.3 [M]-. MS (DCI negative): m/z
1215.9 [M - 2H]-.
crude product was characterized by NMR and MS. H
NMR (CD3OD): δ, ppm 8.92 (d, 3JHH = 4.0 Hz, 2H), 8.56
(d,3JHH = 4.5 Hz, 2H), 8.47 (d,3JHH = 4.0 Hz, 2H), 8.39 (d,
3JHH = 4.5 Hz, 2H). 19F NMR (CD3OD): δ, ppm -136.5 (m,
ortho-F, 4F), -137.0 (m, ortho-F, 2F), -141.7 (m, meta-F,
6F). UV-vis (H2O): λmax, nm 422 (Soret), 578 (Q-band),
610 (Q-band). MS (FAB negative): m/z 837.2 [M - H]-.
The product is not stable at rt and under aerobic atmo-
sphere for extended times, a problem that was resolved
by in situ S-alkylation. The solution obtained from the
reaction of H3(tpfc) with NaHS in DMF was cooled to
rt and 0.5 mL of CH3I (8 mmol) was added, and mixed
under N2 for 30 min. Solvent evaporation and chromato-
graphic treatment (silica gel 60, eluent: CH2Cl2/n-hexane
1/4) yielded the product with p-S-CH3 at all meso aryls.
(yield: 106 mg, 95%). 1H NMR (CDCl3): δ, ppm 9.10 (d,
3JHH = 4.3 Hz, 2H), 8.90 (d, 3JHH = 4.7 Hz, 2H), 8.80 (m,
Synthesis of 13. 50 mg of 1-Cl (0.05 mmol) were dis-
solved in 50 mL CH2Cl2. 150 mg of bis[2-[2-(2-meth-
oxyethoxy)ethoxy]ethyl]amine [12] (0.5 mmol) were
added and the solution was stirred for 3 h. The solution
was washed twice with a solution of HCl (2 M) and then
with distilled water. The solvent was evaporated. PTLC on
silica (eluent: CH2Cl2, then CH2Cl2/EtOH 50:1) afforded
1
13 as a dark green solid (yield: 40 mg, 52%). H NMR
(CD3OD): δ, ppm 9.48 (s, 1H), 8.61 (s, 1H), 8.43 (d, 3JHH
=
4.8 Hz, 1H), 8.25 (d, 3JHH = 4.8 Hz, 1H), 8.18 (d, 3JHH = 4.8
Hz, 1H), 8.15 (d, 3JHH = 4.8 Hz, 1H), 2.70-3.80 (m, 60H).
19F NMR (CD3OD): δ, ppm -135.0 (d, 3JFF = 17.0 Hz, 2F),
-136.7 (m, 4F), -153.8 (t, 3JFF = 20.0 Hz, 1F), -154.7 (t, 3JFF =
3
4H). 19F NMR (CD3OD): δ, ppm -135.4 (dd, JFF = 24.3
4
3
Hz, JFF = 11.7 Hz, 4F; ortho-F), -135.8 (dd, JFF = 24.8
3
4
3
20.0 Hz, 1F), -155.8 (t, JFF = 20.0 Hz, 1F), -161.8 (m,
Hz, JFF = 11.7 Hz, 2F; ortho-F), -138.2 (dd, JFF = 25.0
4
3
2F), -162.6 (m, 2F), -164.6 (m, 2F). UV-vis (MeOH): λmax
,
Hz, JFF = 11.8 Hz, 2F; meta-F), -138.8 (dd, JFF = 24.3
nm (ε, M-1.cm-1) 418 (85,000), 440 (69,000), 638 (39,000).
MS (MALDI positive): m/z 1583.5 [(M - H) + 2Na]+.
Synthesis of 13-Ga. 20 mg of 13 (0.013 mmol) were
dissolved in 10 mL pyridine. 100 mg of anhydrous GaCl3
Hz, JFF = 12.0 Hz, 4F; meta-F). UV-vis (CH2Cl2): λmax,
4
nm 414 (Soret), 562 (Q-band), 608 (Q-band). MS (DCI
positive): m/z 895.2 [M + H]+. MS (DCI negative): m/z
894.2 [M]-.
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 915–923

916
A. MAhAMMeD AnD Z. GrOSS
versatile synthetic methodology for covalent attachment
of functionally-adding moieties to the corrole molecule.
We now demonstrate the utilization of 1-Cl as the com-
mon synthon in all the below outlined examples that are
useful for corrole-based advanced materials.
RESULTS AND DISCUSSION
The most commonly adopted synthetic methodology
for adding functionality (chirality, recognition elements,
electron acceptors, etc.) to porphyrins [13], which has
occasionally also been used on corrole [14], relies on
reactions performed on the C-X (X = OH, NH2, Br, etc.)
bonds of meso-aryl substituents. Frequently encountered
problems are atropoisomerization, harsh reaction condi-
tions, tedious separation of desired products, the need
for non-obviously prepared precursors, and protection
of the inner NH protons by metalation/demetalation
procedures. One highlight of triarylcorrole chemistry is
the finding that electrophilic substitution proceeds with
exceptional selectivity on the directly joined pyrrole
rings that distinguish this special molecular framework
[2]. The most outstanding example is chlorosulfonation
of corrole H3(tpfc), which provides the bis-functionalized
corrole 1-Cl in high yield and excellent selectivity [4].
The accessibility of this corrole is very high, since its
preparation from corrole H3(tpfc) does not require pro-
tection of the inner NH protons and proceeds in effec-
tively quantitative yields under extremely simple reaction
conditions. Most important for the desired uses is that
the hydrolytic stability of the β-pyrrole-attached SO2-Cl
moieties is quite high, while their reactions with amines
occurs almost instantaneously in many cases. This sug-
gests sulfonamidation of corrole 1-Cl as a facile and
Corrole-based donor-acceptor dyads
Porphyrin dyads continue to receive much attention,
mainly as part of ongoing efforts devoted to gaining better
understanding and improved mimicking of the processes
relevant to natural photosynthesis [15]. Many other por-
phyrinoids such as phthalocyanines, subphthalocyanines,
chlorins, and fused porphyrins, have also been used as
part of such dyads as each of these has its characteristic
photophysical properties [16]. Corrole/corrole only and
porphyrin/corrole dyads have been investigated quite
intensively [17], while most recently reported examples
are about dyads comprising free-base corrole and electron
acceptors (such as perylenebisimide, 1,8-naphthalimide,
naphthalene bisimide and fullerene) [18]. Common to
all the above examples (except of fullerene [19]) is the
synthetic approach: preparation of an electron acceptor
that is covalently attached to an aldehyde, which is then
used in the corrole forming reaction. The methodology
that relies on 1-Cl route is conceptually different, as well
as substantially simpler and more versatile. Any amine-
containing electron-accepting molecule may in principle
C6F5
C6F5
C6F5
HN
N
HN
N
HN
NH HN
1-aminoanthraquinone
C6F5
ethylenediamine
N
C6F5
C6F5
C6F5
C6F5
C6F5
NH HN
NH HN
SO2
NH
SO2NH
SO2Cl
O
O
O2S
NH
HNO2S
3
SO2Cl
(74% from 1-Cl)
O
NH2
1-Cl
H2N
phthalic
anhydride
in pyridine
O
5
(76% from 1-Cl)
C6F5
C6F5
pyr
N
Ga
N
GaCl3 in
pyridine
HN
N
N
C6F5
C6F5
C6F5
C6F5
NH HN
N
SO2NH
SO2NH
HNO2S
N
HNO2S
N
N
O
O
O
O
N
O
O
O
O
4
4-Ga
(86% from 4)
(69% from 3)
Scheme 2. Preparative methods for corrole-based dyads: 4, 4-Ga, and 5
Copyright © 2010 World Scientific Publishing Company
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ChlOrOSulfOnAteD COrrOle: A verSAtIle SynthOn fOr ADvAnCeD MAterIAlS
917
be covalently attached to the peripheral substituents of
the preformed corrole.
afforded complex 4-Ga. Figures 1a–1c show the absorp-
tion spectra of these compounds in methanol. Compared
to the spectrum of 3, the spectra 4 and 4-Ga contain a
new band with at λmax at 220 nm, characteristic of the UV
absorption of phthalimide. More detailed spectroscopic
properties of these dyads, as well as the kinetics of intra-
molecular energy and electron transfer therein, are cur-
rently investigated. One focus of the future studies will be
on stronger electron acceptors than simple phthalimide.
We demonstrate the above statement by using 1-Cl
as the precursor for attaching two acceptors, based on
anthraquinone and phthalimide. An anthraquinone moi-
ety was attached in one step by reacting corrole 1-Cl
with 1-aminoanthraquinone. Figure 1d shows the absor-
bance spectrum of this dyad (5) in methanol, which may
be considered as a superimposition of the absorbance of
anthraquinone (λmax = 256 nm) and the corrole. A phthal-
imide moiety was attached in two steps, taking advantage
of the easy preparation of phthalimides via the reactions
of phthalic anhydride with amines. Reaction of 1-Cl
with ethylenediamine provides the bis-amino corrole 3,
whose reaction with phthalic anhydride leads to corrole
4 in high yield. Consecutive metalation of 4 with GaCl3
Carbohydrate-containing corroles (for chirality, rec-
ognition and water-solubility)
The role of saccharides in cell recognition, metabolism,
and cell labeling is well established and conjugation of sac-
charides to potential porphyrin-based drug is an active area
of research [20]. Introduction of sugar moieties into por-
phyrins may be used for inducing water solubility and the
interaction of such derivatives with cell membranes differs
significantly from that of porphyrins that contain water-
solubilizing cationic or anionic moieties [21]. Sugars are
also part of the “chiral pool” [22], whose covalent attach-
ment to complexes of well-established catalytic activity
adds elements of chirality for utilization in asymmetric
catalysis [23]. Porphyrins with sugar moieties have been
prepared indeed, usually being connected by ester, ether
or thioether linkages [24]. For example, reaction of thio-
sugars with tetra(pentafluorophenyl)porphyrin produce
saccharide-porphyrin conjugates in high yield. In vitro
examination of these S-glucosylated photosensitizers in
Hela cells exerted potent photocytotoxicity. They act as not
only water-solubility-enhancing functionalities but also
cellular-uptake-enhancing elements [25]. Despite of the
recent developments regarding the potential of corroles as
novel drug candidates on one hand and the facile synthesis
of many new corroles on the other hand, purified carbohy-
drate-corrole conjugates have not yet been reported [10b].
The preparation of the sugar-corrole conjugate started
by attaching an oxygen-protected aminoglucose to 1-Cl.
The facile reaction of 2-aminotetra-O-acetyl-2-deoxy-
β-D-glucose with 1-Cl produces 6; and hydrolysis with
ammonia in methanol leads to 7 with free hydroxyl groups
(Scheme 3). The CD spectra of complex 6 and 7 (Fig. 2)
are very rich, with the strong absorbances in the visible
demonstrating that the sugar-induced chirality is strongly
sensed by the corrole. The free-base corrole 7 was meta-
lated by cobalt acetate as to produce the cobalt(III) com-
plex 7-Co, but the analogous reaction with GaCl3 did
not yield the gallium(III) complex 7-Ga. That complex
is, however, accessible by inverting the synthetic route:
metalation of 6 with GaCl3 to the gallium(III) complex
6-Ga, followed by hydrolysis of the O-protecting groups
(Scheme 3).
Corroles for avidin-biotin technologies
Fig. 1. Electronic spectra of (a) 3, (b) 4, (c) 4-Ga, and (d) 5, in
MeOH solutions, with the arrows pointing toward the absor-
bance bands of the covalently attached acceptor groups
The exceedingly strong interaction between egg white
derived avidin and the biotin vitamin is the basis of a
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 917–923

918
A. MAhAMMeD AnD Z. GrOSS
C6F5
HN
NH HN
N
C6F5
C6F5
SO2Cl
SO2Cl
1-Cl
2-aminotetra-O-acetyl-2-deoxy-β-D-glucose
C6F5
C6F5
HN
N
HN
N
7 N NH3 in MeOH, rt, 2 days
C6F5
SO2
C6F5
SO2
C6F5
C6F5
NH HN
NH HN
HN
OAc
OAc
HN
OH
OH
O2S
AcO
O2S
NH
NH
OH
HO
AcO
HO
OAc
OAc
O
O
O
O
AcO
HO
OH
7
6
(95% from 6)
(46% from 1-Cl)
AcO
HO
Co(OAc)2·4H2O
GaCl3
C6F5
C6F5
N
N
N
N
M
C6F5
SO2
C6F5
N
N
MeOH,H2O,TEA (2:1:1), rt, 2 days
Ga
C6F5
SO2
C6F5
N
N
HN
HO
OH
OH
O2S
NH
HO
HN
OAc
OAc
OH
O2S
O
NH
AcO
O
AcO
HO
OAc
OAc
OH
O
O
HO
AcO
6-Ga
(84% from 6)
7-Ga: M=Ga (75% from 6-Ga)
7-Co: M=Co (86% from 7)
AcO
Scheme 3. Preparative method for the corrole-glucose conjugate 6 and its metal complexes
technology with broad applications in virtu-
ally all fields of biology and biotechnology
[26]. These include affinity targeting, cross-
linking and immobilization studies, cell
cytometry, blotting technology, drug deliv-
ery, bioaffinity sensors, and asymmetric
bio-catalysis [27]. The general idea of the
approach is that even when biotin is coupled
to other molecules, it can still be recognized
by avidin either as the native protein or in
derivative forms that contain a number of
reporter groups. The mediation through the
Fig. 2. CD spectra of 6 and 7 in methanol
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 918–923

ChlOrOSulfOnAteD COrrOle: A verSAtIle SynthOn fOr ADvAnCeD MAterIAlS
919
C6F5
C6F5
HN
NH HN
N
HN
NH HN
N
Tris(2-aminoethyl)amine
C6F5
C6F5
C6F5
C6F5
SO2
NH
SO2Cl
O2S
HN
SO2Cl
N
1-Cl
(+)-biotin, CDMT, NMM in CH3CN
H2N
8
(19% from 1-Cl)
C6F5
C6F5
HN
N
N
N
Mn(OAc)2·4H2O or FeCl2
C6F5
C6F5
C6F5
C6F5
M
NH HN
N
N
SO2
NH
SO2
NH
O2S
HN
O2S
HN
N
N
HN
OC
HN
OC
S
S
H
H
H
H
HN
NH
HN
NH
O
O
9-Mn: M = Mn (77% from 9)
9-Fe: M = Fe (77% from 9)
9
(60% from 8)
Scheme 4. Preparative method for the corrole-biotin conjugate 9 and its metal complexes
avidin-biotin complex often leads to a dramatic enhance-
curved) line is consistent with an extremely large bind-
ing constant and the saturation is also perfectly consistent
with the known feature of avidin: it is a tetrameric protein
composed of four identical subunits, every subunit has one
binding site for biotin, and all of them are apparently fully
bound at a [9]/[avidin] ratio of 4.
ment of signal and/or sensitivity levels. We now report
the first example of a corrole that is covalently attached
to biotin, as well as its affinity to avidin.
Tris(2-aminoethyl)amine was selected for the above
purpose, utilizing two of its amino group for the sulfonami-
dation reaction with 1-Cl (which produced 8) and the third
one for the amidation reaction of 8 with the carboxylic acid
moiety of biotin (Scheme 4). Such produced biotin-corrole
conjugate 9 was easily metalated by either manganese(II)
acetate or ferrous chloride, leading to 9-Mn and 9-Fe,
respectively. The binding of 9 with avidin was examined
by recording the CD spectra of an avidin solution as a func-
tion of added 9 (Fig. 3a). Since both avidin and biotin does
not absorb visible light and the biotin moity in 9 is very
far from its corrole, the CD spectrum at long wavelengths
(λ > 360 nm) necessarily reflects corrole interactions with
the chiral environment of the folded protein. The ellipticity
(measured at 440 nm) increased linearly with the concen-
tration of 9 and reached saturation when the ratio between
9 and avidin was 4 (Fig. 3b). The straight (rather than
Amino acid-containing corroles
Attachment of amino acid moieties may be used to
improve water solubility of porphyrins and for establish-
ing specific interactions with cell membranes. Porphyrins
coupled with amino acids have been prepared indeed and
some of them have interesting characteristics relevant for
PDT [28]. In one such example, quite a remarkable pho-
tocytotoxicity with visible light irradiation was reported.
There is also one example of a corrole with an attached
amino acid amide. The synthesis of this complex starts
with the preparation of a corrole with one nitrophenyl
substituent (on C10), reduction of the nitro groups and
amidation with the carboxylic acid group of N-protected
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 919–923

920
A. MAhAMMeD AnD Z. GrOSS
Fig. 3. (a) CD spectra of 4 µM avidin phosphate buffer solutions (pH 7.0), with increasing amounts of the biotin-conjugated corrole
9: (1) 0 µM, (2) 4 µM, (3) 8 µM, (4) 12 µM, (5) 16 µM, (6) 20 µM, (7) 28 µM. (b) Ellipticity at 440 nm as a function of the [9]/
[avidin] ratio, with 4 µM avidin
C6F5
HN
NH HN
N
C6F5
C6F5
SO2Cl
SO2Cl
1-Cl
glycine ethyl ester
C6F5
C6F5
HN
NH HN
N
HN
NH HN
N
Na2CO3 in H2O, reflux
C6F5
C6F5
C6F5
C6F5
SO2
NH
SO2
NH
O2S
O2S
HN
NH
CO2Et
CO2H
CO2H
CO2Et
10
(100% from 1-Cl)
11
(84% from 10)
FeCl2·4H2O
C6F5
N
C6F5
N
N
N
Na2CO3 in H2O, reflux
C6F5
Fe
C6F5
Fe
N
C6F5
C6F5
N
N
N
SO2
NH
SO2
NH
O2S
O2S
HN
NH
CO2Et
CO2H
CO2H
11-Fe
(79% from 10-Fe)
CO2Et
10-Fe
(82% from 10)
Scheme 5. Preparative method for the glycine-corrole conjugate 11 and its iron complex
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 920–923

ChlOrOSulfOnAteD COrrOle: A verSAtIle SynthOn fOr ADvAnCeD MAterIAlS
921
C6F5
C6F5
HN
NH HN
N
HN
NH HN
N
L-cysteine ethyl ester
C6F5
C6F5
C6F5
C6F5
SO2
NH
SO2Cl
O2S
SO2Cl
1-Cl
NH
HS
CO2Et
HS
CO2Et
12
(100% from 1-Cl)
Scheme 6. Preparative method for the cysteine-corrole conjugate 12
tyrosine [29]. What we present is a facile and general pro-
cedure that may used for attaching corroles to any amino
acid through the amine terminus, thus leaving behind a
free carboxylic acid moiety.
The above statement is exemplified by the facile reac-
tions of ethyl ester protected glycine and cysteine with
1-Cl. In the first example, the ester group of 10 was easily
hydrolyzed by heating in basic solution as to produce the
free-base 11 (Scheme 5), which is water soluble, bipolar
and of a structure that resembles that of protoporphyrin
IX. Treatment of corrole 10 with ferrous chloride leads to
the iron(III) corrole 10-Fe, which upon hydrolysis yields
11-Fe, a water soluble iron(III) corrole that may be con-
sidered as heme analog by virtue of having two carboxy-
lic acid residues located on two adjacent pyrrole rings.
Compound 12, which has been prepared via the reac-
tion of 1-Cl with L-cysteine ethyl ester (Scheme 6), has
two free thiol groups that may be used for attaching
C6F5
C6F5
HN
N
HN
NH HN
N
bis(3,6,9-trioxadecyl)amine
C6F5
C6F5
C6F5
C6F5
NH HN
SO2
N
SO2Cl
O2S
SO2Cl
O
N
O
1-Cl
O
O
O
O
GaCl3 or Mn(OAc)2·4H2O
O
O
O
O
O
O
13
(52% from 1-Cl)
C6F5
N
N
C6F5
M
C6F5
N
N
SO2
N
O2S
O
N
O
O
O
O
O
O
O
O
O
O
O
13-Ga: M=Ga (87% from 13)
13-Mn: M=Mn (82% from 13)
Scheme 7. Preparative method for the PEGylated corrole conjugate 13 and its metal complexes
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J. Porphyrins Phthalocyanines 2010; 14: 921–923

922
A. MAhAMMeD AnD Z. GrOSS
corroles onto surface electrodes, such as gold, for a large
variety of applications [30].
3. a) Gryko DT. J. Porphyrins Phthalocyanines 2008;
12: 906. b) Koszarna B and Gryko DT. Tetrahedron
Lett. 2006; 47: 6205. c) Aviv-Harel I and Gross Z.
Chem. Eur. J. 2009; 15: 8382. d) Nago TH, Punto-
riero F, Nastasi F, Robeyns K, Meervelt LV, Cam-
pagna S, Dehaen W and Maes W. Chem. Eur. J.
2010; 16: 5691.
4. a) Mahammed A, Goldberg I and Gross Z. Org.
Lett. 2001; 3: 3443. b) For less selective chloro-
sulfonation of other triaryl corroles, see: Nigel-
Etinger I, Mahammed A and Gross Z. Submitted
for publication.
PEGylated corroles (for cellular uptake and water-
solubility)
Poly(ethylene glycol) (PEG) is a water soluble poly-
mer that exhibits protein resistance, low toxicity, and
non-immunogenicity [31]. One of the most popular strat-
egies for increasing the water solubility and therapeu-
tic activity of porphyrin derivatives and other agents is
conjugation with PEG [32]. It has been shown that the
aggregation of PEGylated porphyrin was reduced (due
to the hydrophilic nature of PEG chains), while selec-
tive accumulation in cancer cells increased [33]. While
several PEGylated porphyrin were developed and stud-
ied for PDT [34], we now report the first PEGylated cor-
role. Reaction of bis(3,6,9-trioxadecyl)amine, with 1-Cl
produced 13 which could be metalated as to produce the
corresponding manganese(III) and gallium(III) corroles
13-Mn and 13-Ga, respectively (Scheme 7). The solubil-
ity of the products in water is, however, quite low. Longer
chain PEG’s, which may in principle be prepared by the
same methodology, are apparently required for improved
water solubility.
5. a) Agadjanian H, Ma J, Rentsendorj A, Valluripalli
V, Hwang JY, Mahammed A, Farkas DL, Gray HB,
Gross Z and Medina-Kauwe LK. Proc. Natl. Acad.
Sci. USA 2009; 106: 6105. b) Okun Z, Kupershmidt
L, Amit T, Mandel S, Bar-Am O, Youdim MB and
Gross Z. ACS Chem. Biol. 2009; 4: 910. c) Haber
A, Mahammed A, Fuhrman B, Volkova N, Cole-
man R, Hayek T, Aviram M and Gross Z. Angew.
Chem. Int. Ed. 2008; 47: 7896. d) Kupershmidt L,
Okun Z, Amit T, Mandel S, Saltsman I, Mahammed
A, Bar-Am O, Gross Z and Youdim MB. J. Neuro-
chem. 2009; 113: 363. e) Kanamori A, Catrinescu
MM, Mahammed A, Gross Z and Levin LA. J. Neu-
rochem. 2010: 114: 488. f) Walker D, Chappel C,
Mahammed A, Brunschwig BS, Winkler JR, Gray
HB, Zaban A and Gross Z. J. Porphyrin Phthalocy-
anines 2006; 10: 1259. g)Aviv I and Gross Z. Chem.
Commun. 2007; 1987.
6. a) Saltsman I, Goldberg I and Gross Z. Tetrahedron
Lett. 2003; 44: 5669. b) Mastroianni M, Zhu W, Ste-
fanelli M, Nardis S, Fronczek FR, Smith KM, Ou
Z, Kadish KM and Paolesse R. Inorg. Chem. 2008;
47: 11680. c) Stefanelli M, Mastroianni M, Nardis
S, Licoccia S, Fronczek FR, Smith KM, Zhu W, Ou
Z, Kadish KM and Paolesse R. Inorg. Chem. 2007;
46: 10791. d) Barata JFB, Neves MGPMS, Tome
AC and Cavaleiro JAS. J. Porphyrins Phthalocya-
nines 2009; 13: 415. e) Paolesse R. Synlett. 2008;
15: 2215. f) Hiroto S, Hisaki I, Shinokubo H and
Osuka A. Angew. Chem. Int. Ed. 2005; 44: 6763.
7. a) Ngo TH, Van Rossom W, Dehaen W and Maes W.
Org. Biomol. Chem. 2009; 7: 439. b) Stefanelli M,
Shen J, Zhu W, Mastroianni M, Mandoj F, Nardis
S, Ou Z, Kadish KM, Fronczek FR, Smith KM and
Paolesse R. Inorg. Chem. 2009; 48: 6879. c) Man-
doj F, Nardis S, Pomarico G and Paolesse R. J. Por-
phyrins Phthalocyanines 2008; 12: 19. d) Capar C,
Hansen LK, Conradie J and Ghosh A. J. Porphyrins
Phthalocyanines 2010; 14: 509.
CONCLUSION
We have exemplified the utilization of chlorosulfi-
nated corrole as the common synthon for biotinylation
and PEGylation, and the preparation of donor-acceptor
dyads, as well as corroles with amino acid carbohydrate
head groups located on one pole of the macrocyle. The
majority of the described reactions may be performed
on the free-base corrole, which can later be metalated
for adding additional functionality. Chirality and other
properties of the attached molecules are strongly sensed
by the corrole, which is very promising for advanced
applications.
Acknowledgements
We thank the Deutsche Forschunggemeinschaft (DFG)
for financial support of this research.
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