Dynamic synthesis of a macrocycle containing a porphyrin and an electron donor

Article abstract of DOI:10.1039/b418811j

New macrocycles incorporating a porphyrin and a π electron-rich aromatic were prepared from a dynamic disulfide library. The outcome could be influenced by use of templates. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b418811j

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Dynamic synthesis of a macrocycle containing a porphyrin and an
electron donor{
Amy L. Kieran,a Sofia I. Pascu,a Thibaut Jarrosson,a Maxwell J. Gunterb and Jeremy K. M. Sanders*a
Received (in Cambridge, UK) 15th December 2004, Accepted 20th January 2005
First published as an Advance Article on the web 11th February 2005
DOI: 10.1039/b418811j
New macrocycles incorporating a porphyrin and a p electron-
rich aromatic were prepared from a dynamic disulfide library.
The outcome could be influenced by use of templates.
Supramolecular assemblies have been used in biomimetic photo-
dynamic systems that seek to replicate both rapid electron transfer
processes and efficient charge-separation.1,2 These are fundamental
characteristics of photosynthetic model systems and artificial
photosynthesis devices. While there have been many examples of
covalently-linked donor–acceptor systems,3–5 access to such
structures is often limited by intricate synthesis. Thus, non-
covalently linked donor–acceptor complexes have been investi-
gated as a way to overcome such obstacles.6–8
We have systematically developed super-structured interlocked
porphyrins using conventional chemical approaches and explored
their binding properties.6,9 We now report the efficient synthesis of
a new porphyrin-containing macrocycle assembled by reversible
thiol–disulfide exchange.10,11 The new building block 1 was
synthesised in four steps according to Scheme 1; porphyrins
2H?2 and Zn?2 were obtained via a previously established route.12
Libraries were set up using 5 mM solutions of building blocks 1
and Zn?2 in CHCl3, and 0.2 eq. DBU. Thermodynamic
equilibrium was reached in 5 days, as observed by HPLC. A
minimum of three cyclic products were expected: dimer 3, mixed
dimer Zn?4 and bis-porphyrin dimer Zn?5 (Scheme 2). No
products due solely to naphthyl species were found, although
traces of higher oligomers were observed, in addition to Zn?4 and
Zn?5. Fractions of the two main components Zn?4 and Zn?5
were isolated and MALDI-TOF analysis showed parent ions at
m/z 5 1374.6 for Zn?4 and at m/z 5 2016.9 for Zn?5. By HPLC,
the ratio of the two products was 4:1 heterodimer Zn?4 to
homodimer Zn?5.13 This non-statistical distribution suggests a
Scheme 2 Reaction of a two component library. Conditions: 5 mM
solutions of building blocks 1 and 2H?2 or Zn?2 (1:1 ratio) and 0.2 eq.
DBU.
stabilising interaction that preferentially favours the formation of
macrocycle Zn?4. The same experiment using the free base
porphyrin monomer 2H?2 showed that the heterodimer is again
the favoured product and that larger oligomers are somewhat
more accessible (Table 1).
Templated libraries were set up using 1 eq. or 5 eq. of hexyl-
substituted naphthyldiimide 6 as a guest, and the product
distribution was again monitored by HPLC (Table 1). When the
libraries were equilibrated in the presence of a five-fold excess of 6,
the homoporphyrin dimers M?5 (M 5 2H or Zn) were preferred,
i.e. 53% yield when M 5 Zn and 61% when M 5 2H.
Scheme 1 i) 2-(29-Chloroethoxy)ethanol, K2CO3, MeCN, 82 uC, 98%; ii)
p-toluenesulfonyl chloride (TsCl) 2.2 eq., NEt3 3 eq., 10% dimethyl-
aminopyridine (DMAP), CH2Cl2, 25 uC, 98%; iii) KSAc, MeCN, 82 uC,
33%; iv, NH2NH2?OAc, CH2Cl2, 95%.
The template-containing products are pseudorotaxanes since it
is expected that the naphthyl guest inserts between the porphyrin
planes (for M?5) or the porphyrin plane and the naphthyl cap (for
M?4) to maximise the stabilising p–p interactions.6,14 Since we have
demonstrated earlier15 the use of alkali halides as templates for the
association of crown ethers with similar naphthyl guests, we
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b4/b418811j/
*jkms@cam.ac.uk
1842 | Chem. Commun., 2005, 1842–1844
This journal is ß The Royal Society of Chemistry 2005

View Article Online
N–N axis. In this strapped conformation the C–Hs of the naphthyl
have a close approach to the electron cloud above the plane of the
porphyrin, as indicated by NMR experiments. This geometry
allows the maximisation of attractive interactions whilst minimis-
ing the electron–electron repulsion. The lower carbons of the
Table 1 Yields of the oligomers in porphyrin–naphthoquinol
libraries based on HPLC analysis
Product
Larger
Experiment
Conditions
M?4
M?5
oligomers
˚
naphthyl ring are located at 3.501(1) and 3.511(1) A (Zn?4) and
˚
3.488 and 3.601 A (2H?4) above the best-fit porphyrin planes. This
1
2
3
4
5
6
Zn?2
Zn?2 + 6 (1 eq.)
1 + Zn?2
1 + Zn?2 + 6 (1 eq.)
1 + Zn?2 + 6 (5 eq.)
1 + Zn?2 + 6 (1 eq.) +
LiBr (10 eq.)
1 + Zn?2 + 6 (1 eq.) +
NaBr (10 eq.)
1 + 2H?2
1 + 2H?2 + 6 (1 eq.)
1 + 2H?2 + 6 (5 eq.)
—
—
81
79
47
77
87
96
19
21
53
23
13
4
—
—
—
—
suggests that there is a significant CH–p interaction between the
porphyrin aromatic ring and the naphthyl hydrogens giving edge-
to-face (T-type) p-stacking geometries.14,16,17 The naphthyl ring is
closer to perpendicular to the mean plane of the porphyrin in 2H?4
than in Zn?4, with an angle between the mean plane of the
naphthyl ring and the mean porphyrin plane of 80.33(1)u in the
former vs 64.83(1)u in the latter. In the crystal structures of M?4
the porphyrins pack in a p-stacked fashion, uncapped sides
together, and the naphthyl rings also p-stack with each other.
Unlike Zn?4, where the porphyrins that p-stack are rotated by 90u
with respect to each other, the porphyrins in 2H?4 are not rotated.
7
87
13
—
8
9
10
92
75
39
5
24
61
3
1
—
˚
In each case, the porphyrin planes are offset by ca. 3.5 A in the
classical manner.
investigated here the ability of lithium or sodium cations to
promote the amplification of the receptor Zn?4. While the use of
Li+ did not significantly affect the yield of the heterodimer Zn?4,
the effect of Na+ on the equilibrium composition led to an 8%
increase of the heterodimer Zn?4 at the expense of the homodimer
Zn?5 (Table 1). Li+ is probably too small for the receptor’s cavity.
Both systems reached equilibrium in 2 days instead of 5 as in the
absence of the alkali salt. This is a new mode of templating within
porphyrin libraries and an exciting addition to the tools available
for supramolecular synthesis.
In summary, we have discovered an extremely efficient dynamic
synthesis of a new macrocycle and have shown that the
naphthyldiimide template 6 amplifies the best-fit library members
(with the most effective p–p host–guest stacking) which unexpect-
edly, in this case, were the bis-porphyrin receptors M?5. The
weaker p–p stacking of this guest inside the heterodimer Zn?4 was
strengthened when additional interactions (coordination of Na+
cations to the glycol chains of the receptor) were introduced.
We thank Drs David Watkin and Andrew Cowley for assistance
with crystallography, EPSRC and the RSC Journal Grant Scheme
for funding.
All results achieved on the analytical scale were reproduced on
1
the preparative scale. In solution, H NMR spectra of Zn?4 and
2H?4 indicated highly symmetrical conformations (240 K–340 K,
500 MHz, CDCl3) with a fast rotation of the naphthyl moiety (on
the NMR time-scale). NOE experiments provided evidence that
the ethylene glycol chain and the naphthyl ring are strapping
across the face of the porphyrin. At temperatures below 230 K 1H
NMR spectra indicated ‘closed up’ conformations of Zn?4 and
2H?4. The orientation of naphthoquinol with respect to the
porphyrin plane is closer to perpendicular thus maximising the p–p
interactions. Significant chemical shifts are given in supplementary
materials.{
Amy L. Kieran,a Sofia I. Pascu,a Thibaut Jarrosson,a Maxwell J. Gunterb
and Jeremy K. M. Sanders*a
aDepartment of Chemistry, University of Cambridge, Lensfield Rd.,
Cambridge, UK CB2 1EW. E-mail: jkms@cam.ac.uk;
Fax: +44 1223 336017; Tel: +44 1223 336411
bSchool of Biological, Biomedical and Molecular Sciences, University of
New England, Armidale, NSW 2351, Australia
Notes and references
{ Crystals were grown from a CHCl3 solution of receptor layered with
MeOH. Data were collected at 180 K on a Nonius KappaCCD with
In each case the X-ray structures{ of Zn?4 and 2H?4 confirm
that the ethyloxy chains are strapped over the face of the saddled
porphyrins (Fig. 1). The conformations observed at low tempera-
˚
graphite monochromated Mo Ka radiation (l 5 0.71073 A). The images
were processed with the DENZO and SCALEPACK programs.18 The
structures were solved by direct methods using the program SIR92.19
The refinement (on F) and graphical calculations were performed using the
CRYSTALS20 program suite.
1
ture by H NMR experiments are maintained in the solid-state.
The naphthyl rings are held above the plane of the porphyrin by
the glycol straps, aligned along, although slightly offset from, one
Zn?4 (two independent molecules in the asymmetric unit):
¯
C160H200N8O8S8Zn2, M 5 2750.69, Z 5 2, triclinic, space group P1,
˚
˚
˚
a 5 17.5480(4) A, b 5 19.9870(5) A, c 5 25.2150(9) A, a 5 95.4860(11)u,
3
˚
b 5 99.0310(11)u, c 5 106.4290(13)u, U 5 8285.5(4) A , T 5 180(2) K,
m 5 0.445 mm21. Of 52898 reflections measured, 21019 were independent
(Rint 5 0.15). Final R 5 0.1479 [7822 reflections with I . 3s(I)] and
wR 5 0.1594. Treatment of 0.5 molecules of CH3CN and 1.5 molecules of
H2O (disordered) per asymmetric unit was performed using the procedure
described by Spek et al.21 implemented in PLATON.22 Thus the structure
contains solvent accessible voids of 230.00 A3. Identification of the
1
crystallising solvents is based upon additional chemical evidence from H
NMR.
2H?4 (two independent molecules in the asymmetric unit):
¯
C160H204N8O8S8, M 52623.96, Z 5 2, triclinic, space group P1,
˚
˚
˚
˚
a 5 15.45070(10) A, b 5 18.8773(2) A, c 5 26.9207(3) A, a 5 90.5208(3)u,
3
Fig. 1 Molecular structures of the M?4 receptors (hydrogen atoms and
b 5 99.9292(3)u, c 5 102.8035(4)u, U 5 7532.83(12) A , T 5 180(2) K,
m 5 0.176 mm21. Of 106913 reflections measured, 26438 were independent
hexyl chains are omitted for clarity).
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1842–1844 | 1843

View Article Online
(Rint 5 0.17). Final R 5 0.1055 [12878 reflections with I . 3s(I)] and
wR 5 0.1243. Both Zn?4 and 2H?4, yielded extremely weakly diffracting
crystals; disorder of S-alkyl chains (modelled with refined occupancies and
restraints on distances, vibrations and temperature factors) and hexyl
chains (modelled with restraints on distances, vibrations and temperature
factors) account for the high R factors.
12 (a) A. L. Kieran, A. D. Bond, A. M. Belenguer and J. K. M. Sanders,
Chem. Commun., 2003, 2674; (b) A. L. Kieran, S. I. Pascu, T. Jarrosson
and J. K. M. Sanders, Chem. Commun., 2005, DOI: 10.1039/b417951j.
13 This calculation takes into account the difference in UV absorbance of
the products.
14 C. A. Hunter and J. K. M. Sanders, J. Am. Chem. Soc., 1990, 112,
5525.
15 (a) G. Kaiser, T. Jarrosson, S. Otto, Y. F. Ng, A. D. Bond and J. K.
M. Sanders, Angew. Chem. Int. Ed., 2004, 43, 1959; (b) S. I. Pascu,
T. Jarrosson, C. Naumann, S. Otto and J. K. M. Sanders, New J.
Chem., 2005, 29, 80.
16 J. E. Cochran, T. J. Parrott, B. J. Whitlock and H. W. Whitlock, J. Am.
Chem. Soc., 1992, 114, 2269.
17 J. F. Malone, C. M. Murray, M. H. Charlton, R. Docherty and
A. J. Lavery, J. Chem. Soc., Faraday Trans., 1997, 93, 3429.
18 Z. Otwinowski and W. Minor, Methods in Enzymology, ed. C. N. Carter
Jr. and R. M. Sweet, Academic Press, London, 1996, vol. 276,
p. 307.
CCDC 256715 and 256716. See http://www.rsc.org/suppdata/cc/b4/
b418811j/ for crystallographic data in CIF or other electronic format.
1 D. Gust, T. A. Moore and A. L. Moore, Acc. Chem. Res., 1993, 26, 198.
2 I. Willner and B. Willner, Top. Curr. Chem., 1991, 159, 157.
3 M. R. Wasielewski, Chem. Rev., 1992, 92, 435.
4 J. L. Sessler, B. Wang, S. L. Springs and C. T. Brown, Comprehensive
Supramolecular Chemistry, ed. D. N. Reinhoudt, Pergamon Press,
Oxford, England, 1996.
5 N. P. Redmore, I. V. Rubtsov and M. J. Therein, Inorg. Chem., 2002,
41, 566.
6 M. J. Gunter, Eur. J. Org. Chem., 2004, 1655.
19 A. Altomare, G. Carascano, C. Giacovazzo and A. Guagliardi, J. Appl.
Crystallogr., 1993, 26, 343.
20 (a) D. J. Watkin, C. K. Prout, J. R. Carruthers and P. W. Betteridge,
CRYSTALS, Oxford University, Oxford, UK, 1996; (b)
P. W. Betteridge, J. R. Carruthers, R. I. Cooper, C. K. Prout and
D. J. Watkin, J. Appl. Crystallogr., 2003, 36, 1487.
21 P. V. D. Sluis and A. L. Spek, Acta Crystallogr., 1990, A46, 194.
22 A. L. Spek, in ‘PLATON, A Multipurpose Crystallographic Tool’,
Utrecht University, Utrecht, The Netherlands, 1998.
7 M. Ward, Chem. Soc. Rev., 1997, 26, 365.
8 I. Willner, E. Kaganer, E. Joselevich, H. Durr, E. David, M. J. Gunter
and M. R. Johnston, Coord. Chem. Rev., 1998, 171, 261.
9 M. J. Gunter, T. P. Jeynes, M. R. Johnston, P. Turner and Z. P. Chen,
J. Chem. Soc., Perkin Trans. 1, 1998, 1945.
10 S. J. Rowan, S. J. Cantrill, G. R. L. Cousins, J. K. M. Sanders and
J. F. Stoddart, Angew. Chem. Int. Ed., 2002, 41, 898.
11 S. Otto, R. L. E. Furlan and J. K. M. Sanders, Drug Discovery Today,
2002, 7, 117.
1844 | Chem. Commun., 2005, 1842–1844
This journal is ß The Royal Society of Chemistry 2005