Disulfide-strapped porphyrins for monolayer formation on gold

Article abstract of DOI:10.1021/ol006615i

(equation presented) M = 2H, Zn; R = n - hexyl Porphyrins with a disulfide-containing strap have been prepared as an alternative to dithiols for self-assembled monolayer formation on gold surfaces. The strapped porphyrins have the advantage of greater air

Full text of DOI:10.1021/ol006615i

ORGANIC
LETTERS
2000
Vol. 2, No. 26
4141-4144
Disulfide-Strapped Porphyrins for
Monolayer Formation on Gold
James E. Redman and Jeremy K. M. Sanders*
Cambridge Centre for Molecular Recognition, UniVersity Chemical Laboratory,
Lensfield Road, Cambridge, CB2 1EW, U.K.
jkms@cam.ac.uk
Received September 19, 2000
ABSTRACT
Porphyrins with a disulfide-containing strap have been prepared as an alternative to dithiols for self-assembled monolayer formation on gold
surfaces. The strapped porphyrins have the advantage of greater air stability than their dithiol analogues. Cis and trans atropisomers of a
strapped porphyrin were isolated. Gold electrodes modified with dithiol and disulfide porphyrins were not identical as evidenced by contact
angle or electrochemical measurements.
The attachment of metalloporphyrins to gold surfaces by way
of a gold-sulfur interaction has afforded self-assembled
monolayers (SAMs) with potential applications ranging from
electrocatalysis to the sensing of volatile analytes.1-14 Por-
phyrins carrying a single alkanethiol group are believed to
pack in SAMs in an offset face-to-face manner with the plane
of the porphyrin tilted with respect to the surface normal.9,11,13
However, multiple alkanethiol substituents around the por-
phyrin periphery constrain the porphyrin to lie parallel to
the surface.7-9,11 The monolayer packing has important
consequences for its function, as stacking may block access
to the porphyrin metal center.3,11 Thiol-substituted porphyrins
are known to undergo facile photosensitized aerial oxidation
to disulfides,10,15 a reaction which may be especially prob-
lematic for polythiols due to the formation of insoluble
polymeric products.16 Here we present the synthesis and
properties of porphyrins with a disulfide “strap” intended to
combine the surface binding properties of dithiols with the
greater oxidative stability of disulfides.
(1) Jagessar, R. C.; Tour, J. M. Org. Lett. 2000, 2, 111.
(2) Guo, L.-H.; McLendon, G.; Razafitrimo, H.; Gao, Y. J. Mater. Chem.
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D’Amico, A. Sens. Actuators, B 1998, 47, 70.
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W. Langmuir 1995, 11, 4109.
(8) Hutchison, J. E.; Postlethwaite, T. A.; Murray, R. W. Langmuir 1993,
9, 3277.
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Yoshimura, T.; Uosaki K. Thin Solid Films 1996, 273, 250.
(10) Yuan, H.; Woo, L. K. J. Porphyrins Phthalocyanines 1997, 1, 189.
(11) Zak, J.; Yuan, H.; Ho, M.; Woo, L. K.; Porter M. D. Langmuir
1993, 9, 2772.
We chose to prepare strapped porphyrins by condensation
of a dialdehyde with a dipyrromethane.17,18 Alkyl thioacetate
(15) Collman, J. P.; Groh, S. E. J. Am. Chem. Soc. 1982, 104, 1391.
(12) Akiyama, T.; Imahori, H.; Sakata, Y. Chem. Lett. 1994, 1447.
(13) Imahori, H.; Norieda, H.; Nishimura, Y.; Yamazaki, I.; Higuchi,
K.; Kato, N.; Motohiro, T.; Yamada, H.; Tamaki, K.; Arimura, M.; Sakata,
Y. J. Phys. Chem. B 2000, 104, 1253.
(14) Kondo, T.; Ito, T.; Nomura, S.; Uosaki, K. Thin Solid Films 1996,
284-285, 652.
(16) Wen, L.; Li, M.; Schlenoff, J. B. J. Am. Chem. Soc. 1997, 119,
7726.
(17) Osuka, A.; Kobayashi, F.; Nagata, T.; Maruyama, K. Chem. Lett.
1990, 287.
(18) Osuka, A.; Kobayashi, F.; Maruyama, K. Bull. Chem. Soc. Jpn. 1991,
64, 1213.
10.1021/ol006615i CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/28/2000

substituted benzaldehydes 3 and 7 were prepared according
to Scheme 1 by alkylation of hydroxybenzaldehyde with
shielding region over the face of the porphyrin. The CH2S
resonance is not observed at the typical chemical shift of
2.7 ppm but is shielded and overlaps with the hexyl-H2
resonance at 2.21 ppm as judged by the 12H integral of this
multiplet. A single porphyrin meso resonance is indicative
of a single atropisomer or rapid atropisomerization on the
NMR chemical shift time scale. The monomeric nature of
the product was confirmed by the high-resolution electro-
spray mass spectrum which displayed a molecular ion at m/z
1257.8930 compared to a calculated mass for [M + H]+ of
1257.8925. The zinc metalated derivative Zn-11 was pre-
pared, and the 1H NMR spectrum of this compound clearly
displays the shielded CH2S triplet at 2.07 ppm.
Scheme 1a
a (a) Cs2CO3, HO(CH2)11Br, DMF; (b) TsCl, Et3N, DCM; (c)
KSAc, PEG 400; (d) K2CO3, MeOH; (e) I2, CHCl3.
bromoundecanol, followed by conversion of the alcohol to
a thioacetate19 via a tosylate. The resulting aldehydes could
be used directly for TFA-catalyzed porphyrin synthesis20 to
afford thioacetate-protected porphyrins 9 and 10.
The ortho aryl substituted porphyrin 10 was obtained as
a mixture of cis and trans atropisomers which proved
inseparable on a preparative scale, although their presence
was revealed by TLC and H NMR. 9 and 10 also exist as
atropisomers, although these interconvert sufficiently rapidly
that only a single spot is observed by TLC.
Condensation of 8 with dipyrromethane followed by DDQ
oxidation afforded two major products with very similar Rf
values on silica gel TLC with all common solvent systems.
However, after metalation with zinc, the products were
separated chromatographically, and on the basis of 1H NMR
evidence we propose that these are a pair of cis and trans
atropisomers of Zn-12. Isolated yields of the cis and trans
forms were 25 and 14%, respectively. Inspection of a CPK
model of trans-Zn-12 shows that the strap is long enough
to span the aryl groups around the periphery of the porphyrin
without considerable distortion of the porphyrin but with
some loss of conformational freedom of the strap. The
compound assigned to the cis isomer displayed a shielded
CH2S triplet at 2.48 ppm in the 1H NMR spectrum, whereas
this multiplet occurred at 2.88 ppm in the trans isomer,
consistent with the CPK model which requires the central
portion of the strap to lie in the deshielding region around
the porphyrin periphery. The dispersion of the strap reso-
1
Cleavage of the thioacetate groups of 3 and 7 under basic
conditions, followed by iodine oxidation without isolation
of the intermediate thiol, afforded dialdehydes 4 and 8.
Dialdehyde 4 was condensed with a dipyrromethane using
conditions similar to those used to prepare 9, but at higher
dilution. Oxidation of the porphyrinogen intermediate with
DDQ afforded strapped porphyrin 11 in an isolated yield of
1
53%. Evidence for the cyclic structure is found in the H
NMR spectrum as the strap is constrained to lie in the
(19) Ferraboschi, P.; Fiecchi, A.; Grisenti, P.; Santaniello, E.; Trave, S.
Synth. Commun. 1987, 17, 1569.
(20) Twyman, L. J.; Sanders, J. K. M. Tetrahedron Lett. 1999, 40, 6681.
4142
Org. Lett., Vol. 2, No. 26, 2000

nances is greater in Zn-11 than cis-Zn-12 as in the former
the meta aryl substitution forces the strap to lie on average
closer to the porphyrin plane. No unusual features, such as
a red-shifted Soret band,21 were observed in the UV/visible
spectra of any of these compounds, suggesting that the
porphyrins are not considerably distorted from planarity by
the strap. Although trans-Zn-12 is a crystalline solid, so far
we have been unable to obtain crystals of sufficient quality
for an X-ray diffraction study.
Deprotection of the thioacetate groups of 9 and Zn-9 by
aminolysis22 afforded dithiols 13 and Zn-13. These com-
pounds were found to be sensitive to a combination of light
and oxygen, with solutions developing a precipitate of
presumably polymeric disulfides within several hours of
exposure to ambient conditions. Exclusion of light was found
to substantially slow this oxidation process. Oxidation of
dilute (<0.1 mM) solutions of 13 and deprotected 10, as a
mixture of atropisomers, with I2 in DCM, followed by zinc
metalation, afforded Zn-11 and cis-Zn-12 in isolated yields
1
Figure 1. 400 MHz H NMR spectra of trans-Zn-12 in C2D2Cl4
after heating at 110 °C for (a) 0 min, (b) 28 min, (c) 76 min.
were fitted to a first-order model, and from the average of
two independent determinations rate constants of 0.038 and
0.11 min-1 were obtained for trans-Zn-12 and trans-12,
respectively. The greater rate of atropisomerization of free-
base porphyrins over their zinc counterparts has been noted
by other authors and ascribed to a rigidification of the
porphyrin on zinc metalation.23
Preliminary studies of the structures of adlayers of these
compounds on gold surfaces have been carried out using
water contact angle measurements and electrochemistry.
Details of the experimental procedures have been reported
previously.24 Advancing and receding contact angles are
summarized in Table 1. Layers of 13 and Zn-13 were found
1
of 87 and 9%, respectively. In each case the H NMR
spectrum of the product was identical to that produced by
the dialdehyde route. It seems likely that oxidative cyclization
to trans-Zn-12 is sufficiently slow to allow competition from
polymer formation, accounting for the poor yield of cis-Zn-
12 and the apparent absence of the trans isomer. More rapid
rotation about the meso-aryl bonds of 13 permits conversion
of the trans to the cis atropisomer which is able to cyclize.
The dialdehyde route to 11 is superior as dithiols and
oxidative polymerization are avoided at all stages.
The thermal atropisomerization of cis- and trans-Zn-12
1
was investigated by H NMR spectroscopy. A sample of
trans-Zn-12 in C2D2Cl4 solution was heated, and spectra
were acquired at regular temperature intervals. After several
minutes at 107 °C the resonances of cis-Zn-12 appeared.
The resonances of both species remained sharp at a temper-
ature of 117 °C. After further heating at 117 °C, the
resonances of trans-Zn-12 disappeared entirely and were
replaced with those of cis-Zn-12, indicating that the trans
atropisomer has only kinetic stability.
A sample of trans-Zn-12 was demetalated by treatment
with TFA. The atropisomerization rates of trans-12 and
trans-Zn-12 were measured at 110 °C in C2D2Cl4. 1H NMR
spectra (Figure 1) were quantified by normalization of the
total porphyrin meso integral for each spectrum and integra-
tion of the CH2S resonance of the trans atropisomer. Data
Table 1. Advancing and Receding Water Contact Angles (θa,
θr),a Differential Capacitanceb (C), and Charge-Transfer
Resistanceb (Rct) of Porphyrin-Modified Gold Electrodes
θa/deg
θr/deg
C/µF cm-2
Rct/kΩ
11
Zn -11
cis-Zn -12
trans-Zn -12
13
99 ( 1
92 ( 1
93 ( 3
90 ( 1
105 ( 1
102 ( 2
79 ( 3
63 ( 4
50 ( 6
59 ( 4
54 ( 7
77 ( 2
57 ( 6
0
9.8
10.5
10.3
12.7
5.1
0.8
0.5
0.3
0.3
34
Zn -13
ba r e gold
4.9
39
16
0.08
a A contact angle of 0 indicates a low and ill defined angle. b Errors
estimated as <50%.
(21) Parusel, A. B. J.; Wondimagegn, T.; Ghosh, A. J. Am. Chem. Soc.
2000, 122, 6371.
(22) Yelm, K. E. Tetrahedron Lett. 1999, 40, 1101.
(23) Freitag, R. A.; Whitten, D. G. J. Phys. Chem. 1983, 87, 3918.
(24) Beulen, M. W. J.; Kastenberg, M. I.; van Veggel, F. C. J. M.;
Reinhoudt, D. N. Langmuir 1998, 14, 7463.
to be more hydrophobic than their cyclic analogues 11 and
Zn-11, which implies that structural differences exist between
the layers of the two classes of compounds. To electrochemi-
cally probe the thickness and permeability of the adlayers,
Org. Lett., Vol. 2, No. 26, 2000
4143

the differential capacitance of functionalized electrodes was
measured at -0.35 V with respect to Hg/Hg2SO4 with a 0.1
M NaClO4 electrolyte. Additionally the charge-transfer
resistance of the layers to the Fe(CN)63-/4- redox couple was
investigated by impedance analysis using an equivalent
circuit model.25 The results are also displayed in Table 1.
The dithiol porphyrins display lower capacitance and higher
resistance than their strapped analogues, indicating the former
layers to be thicker and/or less permeable to ions.26
a partially blocked electrode.27 Peaks were absent entirely
when electrodes modified with 13 and Zn-13 were used,
implying that these layers effectively insulate the electrode
from the redox probe. These electrochemical results cor-
roborate the contact angle values which indicate that the
structures of adlayers of the dithiol porphyrins and their
strapped analogues are not identical. The differences may
arise from incomplete binding of dithiols to the surface8,28
or adsorption of disulfide polymers despite care to exclude
light from solutions of the porphyrins during incubation with
gold electrodes to avoid accelerating the oxidation process.
Both sulfur atoms of the strapped compounds will contact
the gold surface simultaneously, so incomplete binding of
sulfur groups is not anticipated. After further surface
characterization and optimization of the adsorption condi-
tions, disulfide-strapped porphyrins should be a valuable
alternative to porphyrin dithiols.
The higher charge-transfer resistance of the layers of 13
and Zn-13 is also reflected in the cyclic voltammograms
(Figure 2) obtained with these modified electrodes and the
In summary, porphyrins with disulfide straps have been
prepared and have the advantage of greater air stability over
their dithiol analogues, and consequently easier handling. Cis
and trans atropisomers of ortho aryl substituted strapped
porphyrins were isolated, and it was demonstrated that the
trans isomer has only kinetic stability. Surface derivatization
experiments have revealed that monolayers of the strapped
porphyrins on gold surfaces are not identical to those
prepared from analogous dithiols.
Acknowledgment. We thank M. W. J. Beulen, F. C. J.
M. van Veggel, and D. N. Reinhoudt for discussions and
use of facilities at the MESA+ research institute. We thank
E. Stulz for MALDI mass spectra. We thank EPSRC, Avecia,
and the European Science Foundation SMARTON program
for funding.
Figure 2. Cyclic voltammograms obtained with bare gold and
3-/4-
porphyrin-modified gold electrodes and the Fe(CN)6
redox
couple: (a) bare Au; (b) Au-11; (c) Au-13. Potential is with
respect to Hg/Hg2SO4.
Supporting Information Available: Experimental details
and characterization of compounds 1-13. This material is
available free of charge via the Internet at http://pubs.acs.org.
Fe(CN)63-/4- redox couple. Relative to a bare gold electrode,
electrodes modified with 11 and Zn-11 displayed a reduced
peak current and increased peak separations, consistent with
OL006615I
(27) Amatore, C.; Save´ant, J. M.; Tessier, D. J. Electroanal. Chem. 1983,
147, 39.
(28) Rieley, H.; Kendall, G. K.; Zemicael, F. W.; Smith, T. L.; Yang, S.
Langmuir 1998, 14, 5147.
(25) Randles, J. E. B. Discuss. Faraday Soc. 1947, 1, 11.
(26) Porter, M. D.; Bright, T. B.; Allara, D. L.; Chidsey, C. E. D. J. Am.
Chem. Soc. 1987, 109, 3559.
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