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E. Scamporrino et al. / Tetrahedron 67 (2011) 3705e3713
methylene bridges, are reported. These compounds, obtained by the
reaction between dibromomethane and 5,15-di[p-(9-methoxytri-
ethylenenoxy)phenyl]-10,20-di[p-hydroxyphenyl]porphyrin, have
a co-facial (nano-clip) or a four wall-box (nano-box) architecture.
Planar isomeric cyclic porphyrin ethers, starting from the 5,10-di
[p-(9-methoxytriethylenenoxy)phenyl]-15,20-di[p-hydroxyphenyl]
porphyrin, were also prepared to verify the dependence of the
spectroscopic data on the molecular arrangement.
The aim of these syntheses was to obtain molecular systems for
the recognition and/or the carriage of bio-molecules. Spectroscopic
data of the nano-clip showed modified soret and Q-bands, with
respect to the monomer and cyclic tetramer. An UVevis titration
allowed verification of the easy and reversible protonation of the
pyrrolic cores which, by electrostatic repulsion, modifies the spatial
distance between the two co-facial porphyrins and, therefore, the
cavity size. This reversible modification could be used to change the
dimer molecule status from open to closed, and facilitate the ac-
commodation or release of suitable chemical species, acting then as
a drug carrier.
the signals of the aeb, a0eb0, ced, eef and geh protons]
experiments.
The 1H NMR spectrum of HO(H2ePCTEG2)OH, reported in Fig 1b
together with the molecular structure of the monomer as an inset,
is similar to that of HO(H2ePTTEG2)OH but, because of its lower
symmetry, the CH pyrrole signals 2, 3, 7, 8, 12, 13, 17, 18 are present
as a characteristic cluster at about 8.8 ppm. Considering the
structure reported as an inset in Fig 1b, the T-ROESY experiment
(omitted for brevity) showed the diagnostic cross-peak correlations
between protons ceb; a0e(17, 18); ae(7, 8); a0e(2, 13) and ae(3, 12)
whereas the COSY experiment (omitted for brevity also) high-
lighted the cross-peak correlations between aeb, a0eb0, ced; eef
and geh protons. All the data indicate HO(H2ePTTEG2)OH and the
HO(H2-PCTEG2)OH as the third and the fourth coloured products,
respectively, eluted from the chromatographic column.
To promote the formation of oligomeric species, the syntheses of
cyclic porphyrins were performed by reacting HO(H2ePTTEG2)OH
or HO(H2ePCTEG2)OH with dibromomethane in diluted conditions
(see Experimental part).
The tetrameric porphyrin molecule (nano-box) could also be
used as a drug carrier, forming an inclusion complex with macro-
molecular drugs, or as a nano-reactor, for the peculiar nano-space
conditions inside the box. In this case, 1H NMR spectroscopic
analysis showed a high-field shift of the aromatic and ether protons
present in the upper and lower box rims as a specific characteristic
of this molecular structure.
These compounds differ from previous analogous porphyrinic
systems14e17 in that their totally covalent structure makes them
more versatile potential macromolecular tools.
MALDI-TOF mass spectra of the final products of both reactions
between dibromemethane and HO(H2ePTTEG2)OH or HO
(H2ePCTEG2)OH are showed in Fig. 2.
Both spectra only show signals corresponding to the molecular
ions of cyclic cy-[Oe(H2ePTTEG2)eOeCH2e]n and or cy-[Oe
(H2ePCTEG2)eOeCH2e]n oligomers (Scheme 1, with n¼2e8)
detected as MHþ (more intense signals, m/z values and composi-
tions are reported in the spectra), MNaþ and MKþ species. In par-
ticular, the peak of the cyclic tetramer is the most abundant species
formed in the reaction with 10,20-di[p-hydroxyphenyl]porphyrin
(Fig. 2a) whereas the cyclic dimer is the most abundant species
formed when 15,20-di[p-hydroxyphenyl]porphyrin is used
(Fig. 2b).
2. Results and discussion
The synthesis of cyclic oligomers containing porphyrin units in-
volved the use of 5,15-di[p-(9-methoxytriethyleneoxy)phenyl]-
10,20-di[p-hydroxyphenyl]porphyrin [indicated as HO(H2ePTTEG2)
OH] or 5,10-di[p-(9-methoxytriethyleneoxy)phenyl]-15,20-di[p-
hydroxyphenyl]porphyrin [indicated as HO(H2ePCTEG2)OH] in turn
obtained by the reaction between tetrakis-p-(hydroxyphenyl)por-
phyrin and 9-methyltriethyleneoxy chloride (see Experimental
section).
Pure HO(H2ePTTEG2)OH and HO(H2ePCTEG2)OH were col-
lected by chromatographic separation and their exact identification
was achieved examining their MALDI-TOF mass spectrometric and
NMR spectra. In Fig. 1, the 1H NMR spectra of the third and fourth
coloured product eluted from the chromatographic column are
compared which, both with a molecular ion at m/z 971 (as MHþ),
were identified as the two isomeric 10,20- and 15,20-di(p-
hydroxyphenyl)porphyrin derivatives.
On the basis of some marked differences, spectrum (a) was
assigned as the centre-symmetrical [HO(H2ePTTEG2)OH] isomer
(see inset in Fig. 1a) for which the following characteristic signals
have been recorded: a signal at 8.87 ppm (8H, pyrrole protons 2, 3,
7, 8, 12, 13, 17, 18); a doublet at 8.12 ppm (4H, phenyl protons a);
a doublet at 8.08 ppm (4H, phenyl protons a0); a doublet at 7.31 (4H,
CH phenyl protons b); a doublet at 7.23 (4H, CH phenyl protons b0);
a broad triplet at 4.42 ppm (4H, methylene protons c); broad triplet
at 4.045 ppm (4H, methylene protons d); four broad triplets, range
3.86e3.72 ppm (16H, methylenes e, f, g, h); a singlet at 3.42 ppm
Pure oligomers were obtained by chromatographic column
fractionation and, as an example, the MALDI-TOF spectra of cyclic
methylene-ether dimer cy-[Oe(H2ePCTEG2)eOeCH2e]2 (obtained
with a yield of 30%) and cyclic methylene-ether tetramer cy-[Oe
(H2ePTTEG2)eOeCH2e]4 (yield of 18%) are shown in Fig. 3a and b,
respectively.
The structure of cy-[Oe(H2ePCTEG2)eOeCH2e]2 was con-
firmed by 1H NMR, COSY and T-ROESY experiments. In particular, as
reported in Fig. 4, the 1H NMR spectrum shows the following sig-
nals (for the assignments see Scheme 2): a doublet at 9.13 ppm (4H,
CeH pyrrole protons 8, 17); a doublet at 8.99 ppm (4H, CeH pyrrole
protons 7, 18); a singlet at 8.93 ppm (4H, CeH pyrrole protons 2, 3);
a singlet at 8.72 ppm (4H, CeH pyrrole protons 12, 13); a doublet at
8.22 ppm (8H, phenyl protons a0); a doublet at 8.19 ppm (8H,
phenyl protons a); a doublet at 7.69 (8H, phenyl protons b0);
a doublet at 7.38 (8H, phenyl protons b); a singlet at 6.41 ppm (4H,
methylene bridge protons c0); a broad triplet at 4.48 ppm (8H,
methylene protons c); a triplet at 4.08 ppm (8H, methylene protons
d); a triplet, range 3.89e3.63 ppm (32H, methylene protons e, f, g,
h); a singlet at 3.44 ppm (12H methyl protons
ꢀ2.73 ppm (4H, NeH pyrrole protons 21, 22).
u); a singlet at
The 1H NMR signal attributions were supported by T-ROESY
[Supplementary data, Fig. 1 in which the cross-peaks correlation
between protons ae(2,3); ae(7,18); bec; a0e(8,17); a0e(12,13);
b0ec0 are shown] and COSY [Supplementary data, Fig. 2 that shows
the cross-peaks correlation between protons aeb; ced; (7,18)e
(8,17) and a0eb0] experiments.
(6H, terminal methyl groups
u
); a singlet at ꢀ2.78 ppm (2H, NeH
pyrrole protons 21, 22). In particular, the collapse of the doublet
signals can be observed due to 2e3, 7e8, 12e13 and 17e18 in the
same unresolved peak (at 8.87 ppm).
The 1H NMR spectrum of cy-[Oe(H2ePTTEG2)eOeCH2e]4, Fig 5,
shows some signals having anomalous chemical shift values. In
particular (for the assignments see Scheme 3): a doublet at
8.80 ppm (16H, CeH pyrrole protons 8, 12e2, 18); a doublet at
8.29 ppm (16H, phenyl protons a0); a doublet at 8.24 ppm (16H,
CeH pyrrole protons 3, 7e13, 17); a doublet at 7.68 ppm (16H,
phenyl protons b0); a broad peak at 6.83 ppm (16H, phenyl protons
These assignments are also supported by T-ROESY [omitted for
brevity, which shows the diagnostic cross-peak correlations be-
tween protons ceb; ae(3, 7, 13, 17) and a0e(8, 12, 2, 18)] and COSY
[omitted for brevity, which shows cross-peak correlations between