Unsymmetrical porphyrins: the role of meso-substituents on their physical properties

Article abstract of DOI:10.1142/S1088424612500332

The synthesis of one-step meso-porphyrins type A_xB_y containing alkyl and pyridyl groups is described. An initial assess of the amphiphilic proprieties were determined by its log K_ow using fluorescence detection techniques and values from 1.42 to 2.15 were observed. The melting points of this set of porphyrins was determined and a strong effect of the number and size of the meso-alkyl chain is ascribed.

Full text of DOI:10.1142/S1088424612500332

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2012; 16: 290–296
DOI: 10.1142/S1088424612500332
Published at http://www.worldscinet.com/jpp/
Unsymmetrical porphyrins: the role of meso-substituents
on their physical properties
César A. Henriques , Nuno P.F. Gonçalves , Artur R. Abreu*a,b◊, Mário J.F. Calvetea
a
a,b
a
and Mariette M. Pereira*
a
Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal
Currently at Luzitin, SA, Rua Bayer, São Martinho do Bispo, 3004-535 Coimbra, Portugal
b
Received 2 December 2011
Accepted 4 January 2012
ABSTRACT: The synthesis of one-step meso-porphyrins type A B containing alkyl and pyridyl groups
x
y
is described. An initial assess of the amphiphilic proprieties were determined by its log Kow using
fluorescence detection techniques and values from 1.42 to 2.15 were observed. The melting points of
this set of porphyrins was determined and a strong effect of the number and size of the meso-alkyl chain
is ascribed.
KEYWORDS: unsymmetrical porphyrins, meso-alkyl substituents, meso-pyridyl substituents, octanol/
water coefficients.
confer a low melting point in the same system, continues
to be somehow a synthetic challenge.
INTRODUCTION
Porphyrins and related compounds are ubiquitous
in nature, being responsible for several biological
energy centers or carrier transport. In the last 50 years
an enormous number of applications for porphyrins,
both natural and synthetic, from catalysts [1, 2] to
molecular devices [3], optoelectronics [4, 5], as well
as photodynamic therapy (PDT) sensitizers [6–9] have
been described. Porphyrins are planar aromatic systems
and tend to form stacks and aggregates inducing low
solubility, high crystallinity, and high melting point
This type of synthesis involves pyrrol condensation
with a mixture of different and appropriate aldehydes
[15–18] or through subsequent derivatization of
some peripheral functions at the meso-position of the
porphyrin ring [18, 19]. Both strategies permit obtaining
porphyrins that combine different characteristics in one
single molecule, therefore facilitating the preparation
of compounds that bear appropriate feature for any
given application. Subsequent use of such tetrapyrrolic
macrocycles in the preparation of more complex
materials depends on a comprehensive understanding of
the contribution of meso-substituents in unsymmetrical
porphyrins in physical and photophysical properties.
Based on our interest in unsymmetrical porphyrins,
here we envisaged the first approach, using both
substituted alkyl (dodecanal, tetradecanal) and 4-pyridine
carboxyaldehyde, using the very straightforward
nitrobenzene method [20, 21], managing not only to
obtain a set of low melting point, neutral porphyrins,
but also to identify and fully characterizing their
photophysical properties.
[
10, 11]. As consequence, for the effective utilization
of porphyrins as functional materials, and based on its
relatively uncomplicated synthetic preparation, it is
possible to endeavor strategies capable of modulate their
electronic, chemical and thermal properties [11]. Several
porphyrins, liquid at room temperature [11–13] (as well
as phthalocyanines [14], their most known tetrapyrrolic
relatives), have been reported. Nevertheless, the design
and synthesis of low melting point porphyrins, (< ꢀ1 00 °C),
containing substituents both polar and non-polar that can

SPP full member in good standing
Their photochemical characterization, evaluation
of their polarity in terms of n-octanol/water partition
coefficients (KOW) was also pursued. This contribution
is expected to help understanding the effect of
*
Correspondence to: Artur R. Abreu, email: aabreu@luzitin.pt
and Mariette M. Pereira, email: mmpereira@qui.uc.pt, tel:
351 239854474, fax: +351 239827703
+
Copyright © 2012 World Scientific Publishing Company

UNSYMMETRICAL PORPHYRINS: THE ROLE OF MESO-SUBSTITUENTS ON THEIR PHYSICAL PROPERTIES
291
meso-substituents, concomitantly allowing future design
of new porphyrins with suitable properties for a number
of applications.
each one was subjected to preparative thin layer
chromatography (PrepTLC), using the corresponding
adequate eluent mixture. The data of the meso-
tetra(undecyl)porphyrin (1) and meso-tetra(4-pyridyl)
porphyrin (6) are in agreement with the literature [12, 23].
EXPERIMENTAL
5
-(4-pyridyl)-10,15,20-tri(undecyl)porphyrin
(
2). Eluent mixture PrepTLC (dichloromethane). Yield
General
(71.9 mg, 1.2% using variant A; 245.3 mg, 3.9% using
variant B); mp 83–86 °C. MS (ESI-TOF): m/z 850.6721
UV-visible absorption spectra were recorded on a
Hitachi U-2010 using quartz cells. The molar absorption
coefficients were determined using cyclohexane as
solvent. The fluorescence spectra for the determination of
the 1-octanol/water partition coefficient and fluorescence
quantum yields were acquire on a Spex Fluorolog 3
spectrophotometer. The MALDI-TOF MS data were
acquired using a Bruker Daltonics flex Analysis apparatus.
Melting points were measured on an Electrothermal
+
1
[
M + H] calcd. for C H N 850.6721. H NMR (400
5
8
84
5
MHz, CDCl ): d, ppm 9.51 (dd, J = 13.8, 4.7 Hz, 4H, H ),
3
b
9
4
.40 (d, J = 4.8 Hz, 2H, H ), 8.93 (s, 2H, H ), 8.72 (d, J =
b
o
.6 Hz, 2H, H ), 8.09 (d, J = 4.7 Hz, 2H, H ), 5.04-4.88
b
m
(m, 6H, CH ), 2.60–2.45 (m, 6H, CH ), 1.88–1.74 (m,
2
2
6
H, CH ), 1.60–1.47 (m, 6H, CH ), 1.40–1.18 (m, 36H,
2 2
CH ), 0.88 (t, J = 8 Hz, 9H, CH ), -2.69 (s, 2H, NH).
2
3
-
1
-1
UV-vis (cyclohexane): l , nm (e, M .cm ) 416 (2.0 ×
0 ), 517 (8.7 × 10 ), 550 (5.4 × 10 ), 597 (2.4 × 10 ), 657
3
max
5
3
3
3
1
(
1
capillary melting point non calibrated apparatus. H NMR
2.7 × 10 ).
,15-di(4-pyridyl)-10,20-di(undecyl)porphyrin (3).
Eluent mixture PrepTLC (dichloromethane/ethyl acetate
:1). Yield (<0.01%, using variant A; 199.5 mg, 3.5%
using variant B); mp 73–74 °C. MS (ESI-TOF): m/z
spectra were recorded on a 400 MHz Brucker-Amx.
All solvents used in the synthesis of the meso-
substituted porphyrin were purified by standard methods
before use [22]. Dichloromethane, chloroform and ethyl
acetate used in column silica gel chromatography were
dried before use. All reactants used in the synthesis of
the meso-substituted porphyrin were purchased
from Sigma and used as received. 1-octanol used for
determination of the 1-octanol/water coefficient partition
was obtained from Merck. Toluene and cyclohexane used
in the spectroscopic studies were acquired from Sigma.
5
5
+
1
7
73.5232 [M + H] calcd. for C H N 773.5265. H
5
2
65
6
NMR (400 MHz, CDCl ): d, ppm 9.47 (d, J = 4.9 Hz,
3
2
2
8
4
H, H ), 9.05 (d, J = 5.8 Hz, 2H, H ), 8.80 (d, J = 4.9 Hz,
b
o
H, H ), 8.18 (dd, J = 4.3 Hz, 1.6 Hz, 2H, H ), 4.95 (t, J =
b
m
.0 Hz, 4H, CH ), 2.55–2.46 (m, 4H, CH ), 1.82–1.73 (m,
2
2
H,CH ), 1.54–1.46 (m, 4H, CH ), 1.39–1.18 (m, 24H,
2
2
CH ), 0.88 (t, J = 8.0 Hz, 6H, CH ), -2.75 (s, 2H, NH).
2
3
-1
-1
UV-vis (cyclohexane): l , nm (e, M .cm ) 415 (1.9 ×
max
Synthesis
5
4
3
3
1
0 ), 514 (1.0 × 10 ), 547 (5.1 × 10 ), 594 (2.7 × 10 ), 653
3
Synthesis of porphyrins 1–11 was carried out by
the nitrobenzene method [21] in which two different
aldehyde mixture ratios were used and here described
as alkyl aldehyde/4-pyridinecarboxaldehyde ratio (3:1 =
variant A; 4:1 = variant B).
The condensation of the mixture of corresponding
alkyl aldehyde (22 mmol for variant A; 29.4 mmol
for variant B), 0.7 mL 4-pyridinecarboxaldehyde (7.35
mmol) with 2 mL pyrrol (29.4 mmol), in a mixture of
acetic acid (105 mL, 1.8 mol) and nitrobenzene (53 mL,
(2.8 × 10 ).
5,10-di(4-pyridyl)-15,20-di(undecyl)porphyrin (4).
Eluent mixture PrepTLC (ethyl acetate). Yield (29.4 mg,
0.5% using variantA; 114.8 mg, 2.0% using variant B); mp
+
153–156 °C. MS (ESI-TOF): m/z 773.5291 [M + H] calcd.
1
for C H N 773.5265. H NMR (400 MHz, CDCl ): d,
52
65
6
3
ppm 9.60 (s, 2H, H ), 9.50 (d, J = 4.7 Hz, 2H, H ), 8.98 (s,
b
b
4H, H ), 8.80 (d, J = 4.4 Hz, 2H, H ), 8.71 (s, 2H, H ), 8.12
o
b
b
(d, J = 5.2 Hz, 4H, H ), 5.02 (t, J = 8 Hz, 4H, CH ), 2.62–
m
2
2.52 (m, 4H, CH ), 1.85–1.80 (m, 4H, CH ), 1.60–1.48 (m,
2
2
0
.5 mol) was carried out at 130 °C (3 h). The reaction
4H, CH ), 1.40–1.18 (m, 24H, CH ), 0.85 (t, J = 8 Hz, 6H,
2
2
was cooled till ~65 °C and the reflux condenser was
substituted by a distillation apparatus, for low pressure
solvents removal. A pre-column chromatography eluting
with an increasing gradient, starting with a petroleum
ether/dichloromethane (2:1) mixture to ethyl acetate/
methanol (9:1) mixture allowed separating the statistical
products from the typical oligomeric and polymeric dark
impurities. In order to obtain pure porphyrin fractions,
second column purification was performed with the same
increasing solvent gradient, allowing the isolation of six
fractions, regardless from the variant or alkyl aldehyde
used, the all possible statistical products.
CH ), -2.74 (s, 2H, NH). UV-vis (cyclohexane): lmax, nm
-1 -1 5 3
3
(e, M .cm ) 415 (1.7 × 10 ), 515 (8.8 × 10 ), 548 (4.9 ×
3
3
3
10 ), 595 (2.9 × 10 ), 652 (2.3 × 10 ).
5,10,15-tri(4-pyridyl)-20-(undecyl)porphyrin (5).
Eluent mixture PrepTLC (ethyl acetate/methanol 18:1).
Yield (56.6 mg, 1.1% using variant A; 26.5 mg, 0.5%
using variant B); mp 227–228 °C. MS (ESI-TOF):
+
m/z 696.3806 [M + H] calcd. for C H N 696.3809.
4
6
46
7
1
H NMR (400 MHz, CDCl ): d, ppm 9.56 (d, J = 4.7 Hz,
3
2H, H ), 9.01 (s, 6H, H ), 8.88 (d, J = 4.6 Hz, 2H, H ),
b
o
b
8.79 (s, 4H, H ), 8.13 (dd, J = 10.7, 5.1 Hz, 4H, H ), 5.04
b
m
(t, J = 8 Hz, 2H, CH ), 2.60–2.55 (m, 2H, CH ), 1.91–
2
2
Itshouldbeemphasizedthattoavoidanycontamination
of each fraction with previous or subsequent fractions,
1.77 (m, 2H, CH ),1.57–1.47 (m, 2H, CH ), 1.49–1.19
2
2
(m, 14H, CH ), 0.87 (t, J = 8 Hz, 3H, CH ), -2.83 (s, 2H,
2
3
Copyright © 2012 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2012; 16: 291–296

292
C.A. HENRIQUES ET AL.
-
1
-1
NH). UV-vis (cyclohexane): l , nm (e, M .cm ) 414
Yield (60.6 mg, 1.2% using variant A; 43 mg, 0.8%
max
4
3
3
(
9.9 × 10 ), 512 (5.6 × 10 ), 544 (1.4 × 10 ), 590 (1.8 ×
using variant B); mp 249–251 °C. MS (ESI-TOF): m/z
3
2
+
1
1
0 ), 648 (9.8 × 10 ).
724.4088 [M + H] calcd. for C H N 724.4122. H
4
8
50
7
Meso-tetra(tridecyl)porphyrin (7). Eluent mixture
PrepTLC (chloroform/n-hexane 2:1). Yield (4.1 mg,
.4% using variantA; 24.9 mg, 0.3% using variant B); mp
NMR (400 MHz, CDCl ): d, ppm 9.56 (d, J = 4.8 Hz,
3
2H, H ), 9.05 (t, J = 6.5 Hz, 6H, H ), 8.88 (d, J = 4.7 Hz,
b
o
0
2H, H ), 8.80 (s, 4H, H ), 8.15 (dd, J = 10.4, 5.5 Hz,
b
b
+
7
2–74 °C. MS (ESI-TOF): m/z 1039.9407 [M + H] calcd.
6H, H ), 5.05 (dd, J = 14.8, 7.0 Hz, 2H, CH ), 2.60–2.48
m
2
1
for C H N 1039.9429. H NMR (400 MHz, CDCl ): d,
(m, 2H, CH ), 1.88–1.70 (m, 2H, CH ), 1.59–1.45 (m,
46
46
7
3
2
2
ppm 9.46 (s, 8H, H ), 4.97 (t, J = 8 Hz, 8H, CH ), 2.59–
2H), 1.32–1.18 (m, 16H, CH ), 0.86 (t, J = 6.7 Hz, 3H,
b
2
2
2
.41 (m, 8H, CH ), 1.89–1.74 (m, 8H, CH ), 1.58–1.48
CH ), -2.82 (s, 2H, NH). UV-vis (cyclohexane): lmax, nm
2
2
3
-1
-1
5
3
(
m, 8H, CH ), 1.40–1.20 (m, 64H, CH ), 0.88 (t, J = 13.3
(e, M .cm ) 414 (1.1 × 10 ), 512 (6.0 × 10 ), 544 (2.6 ×
3 3 3
2
2
Hz, 12H), -2.63 (s, 2H, NH). UV-vis (cyclohexane): lmax,
10 ), 590 (1.8 × 10 ), 648 (1.0 × 10 ).
-1
-1
4
4
nm (e, M .cm ) 416 (2.8 × 10 ), 520 (1.1 × 10 ), 552
3
3
3
(
9.0 × 10 ), 602 (3.1 × 10 ), 662 (4.9 × 10 ).
-(4-pyridyl)-10,15,20-tri(tridecyl)porphyrin (8).
Eluent mixture PrepTLC (chloroform). Yield (85.0 mg,
Octanol/water partition coefficients
5
Octanol/water partition coefficients were measured
following shake-flask method with minor modifications
[24, 25]. Six porphyrin solutions were prepared using
a mixture of ethanol/PBS (70:30) as solvent, with
1
7
.3% using variant A; 0.4 mg, 5.8% using variant B); mp
+
5–77 °C. MS (ESI-TOF): m/z 934.7676 [M + H] calcd.
1
for C H N 934.7660. H NMR (400 MHz, CDCl ): d,
6
4
96
5
3
-8
-6
concentrations between 10 e 10 M, measured at room
temperature (~25 °C), with PBS pH = 7.4. Six more
porphyrin solutions in the same range of concentrations
were also prepared using ethanol/1-octanol (70:30)
mixture as solvent. The initial fluorescence spectra
were taken and the calibration curve for the coefficient
determination plotted. Partition coefficients were
determined by Equation 1:
ppm 9.52 (dd, J = 13.8, 4.5 Hz, 4H, H ), 9.41 (d, J =
b
4
4
.7 Hz, 2H, H ), 9.01 (d, J = 4.7 Hz, 2H, H ), 8.74 (d, J =
b
o
.6 Hz, 2H, H ), 8.12 (d, J = 4.9 Hz, 2H, H ), 4.96 (t,
b
m
J = 8 Hz, 6H, CH ), 2.62–2.42 (m, 6H, CH ), 1.88–1.74
2
2
(
m, 6H, CH ), 1.60–1.46 (m, 6H, CH ), 1.43–1.19 (m,
2
2
4
8H, CH ), 0.87 (t, J = 5.8 Hz, 9H), -2.67 (s, 2H, NH).
-1 -1
2
UV-vis (cyclohexane): l , nm (e, M .cm ) 416 (2.9 ×
max
5
4
3
3
1
6
0 ), 517 (1.2 × 10 ), 550 (7.1 × 10 ), 601 (2.4 × 10 ),
3
57 (3.5 × 10 ).
Co
5
,15-di(4-pyridyl)-10,20-di(tridecyl)porphyrin (9).
P =
(1)
Cw
Eluent mixture PrepTLC (chloroform/ethyl acetate 5:1).
Yield (25.0 mg, 0.4% using variant A; 185.7 mg, 3.1%
using variant B); mp 72–73 °C. MS (ESI-TOF): m/z
where C and C represent the absolute concentration
o
w
+
1
of porphyrin in organic (octanol) and aqueous (PBS)
phases, respectively.
8
29.5915 [M + H] calcd. for C H N 829.5891. H
56
73
6
NMR (400 MHz, CDCl ): d, ppm 9.48 (d, J = 4.8 Hz, 4H,
3
H ), 9.05 (d, J = 4.7 Hz, 4H, H ), 8.81 (d, J = 4.7 Hz, 4H,
b
o
Molar absorption coefficients and fluorescence quan-
tum yields
H ), 8.18 (d, J = 5.3 Hz, 4H, H ), 4.97 (t, J = 8 Hz, 4H,
b
m
CH ), 2.59–2.45 (m, 4H, CH ), 1.83–1.73 (m, 4H, CH ),
2
2
2
1
.54–1.45 (m, 4H, CH ), 1.40–1.18 (m, 32H, CH ), 0.87 (t,
2
2
Molar absorption coefficients were determined using
solutions with concentration between 10 e 10 M,
therefore following Beer–Lambert law, A = ebc.
Fluorescence emission spectra were taken at room
temperature and fluorescence quantum yield was
calculated following a literature method [26], whose
reference used was meso-tetraphenyl porphyrin (TPP)
J = 8 Hz, 6H, CH ), -2.75 (s, 6H). UV-vis (cyclohexane):
lmax, nm (e, M .cm ) 415 (1.2 × 10 ), 514 (6.0 × 10 ), 547
-5
-7
3
-1
-1
5
3
3
3
3
(
2.9 × 10 ), 594 (1.4 × 10 ), 653 (1.4 × 10 ).
,10-di(4-pyridyl)-15,20-di(tridecyl)porphyrin
10). Eluent mixture PrepTLC (chloroform/ethyl acetate
:1). Yield (66.4 mg, 1.1% using variant A; 83 mg, 1.4%
using variant B); mp 141–143 °C. MS (ESI-TOF): m/z
5
(
5
in toluene (F = 0.11) [27]. Values were determined
F
+
1
8
29.5858 [M + H] calcd. for C H N 829.5892. H
5
6
73
6
using solutions with concentrations assuring that the
absorbance had its maximum of 0.02 a.u., using toluene
as solvent.
NMR (400 MHz, CDCl ): d, ppm 9.57 (s, 2H, H ), 9.48
3
b
(
(
5
d, J = 4.7 Hz, 2H, H ), 9.01 (d, J = 5.0 Hz, 4H, H ), 8.80
b
o
d, J = 4.5 Hz, 2H, H ), 8.71 (s, 2H, H ), 8.12 (d, J =
b
b
Comparison between spectral reference area and
.4 Hz, 4H, H ), 4.98 (t, J = 8 Hz, 4H, CH ), 2.60–2.49
m
2
sample spectral emission gave each value of F , by
F
(
m, 4H, CH ), 1.87–1.75 (m, 4H, CH ), 1.58–1.48 (m,
2
2
Equation (2) [28]:
4
6
H, CH ), 1.43–1.18 (m, 32H, CH ), 0.87 (t, J = 6.5 Hz,
2
2
H, CH ), -2.75 (s, 2H, NH). UV-vis (cyclohexane): lmax,
3
ΦF(sample)
ΦF(TPP)
Area(sample)
Area(TPP)
η2(sample)
η2(TPP)
Abs(TPP)
-
1
-1
5
3
nm (e, M .cm ) 415 (2.0 × 10 ), 515 (9.5 × 10 ), 548
) =
×
3
3
3
Abs(sample)
(
4.8 × 10 ), 594 (2.7 × 10 ), 652 (1.9 × 10 ).
,10,15-tri(4-pyridyl)-20-(tridecyl)porphyrin (11).
Eluent mixture PrepTLC (ethyl acetate/methanol 18:1).
5
×
(2)
Copyright © 2012 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2012; 16: 292–296

UNSYMMETRICAL PORPHYRINS: THE ROLE OF MESO-SUBSTITUENTS ON THEIR PHYSICAL PROPERTIES
293
where h is solvent refractive index in which both the
compound and the reference are dissolved, Abs is the
absorbance measured at the excitation wavelength.
In order to analyze the effect of the alkyl side chain
size on the physical properties of these compounds,
the same methodology was applied for the synthesis
of porphyrins 7–11, where pyrrol, tetradecanal and
4
-pyridinecarboxyaldehyde were mixed and heated up
RESULTS AND DISCUSSION
for 1 h at 140 °C, using the nitrobenzene method.
For the synthesis of this family of porphyrins the
tetradecanal/4-pyridinecarboxaldehye ratios were also
tested in 3:1 and 4:1 fashion, and once again an yield
increase was observed for the porphyrins containing one
(8, 5.8% yield) and two pyridyl fragments at the meso-
position in opposite (9, 3.1% yield) and adjacent (10,
1.4% yield) positions of the macrocycle.After preparative
TLC separation, it was possible to isolate compounds 6
and 7–11 in the yields reported on Table 2 (entries 2, 4, 6,
8, 10 and 12, respectively).
Unsymmetrical meso-substituted porphyrins
The synthetic strategies described in the literature
[
18] to obtain A B unsymmetrical porphyrins
x y
involves the condensation of pyrrol with two different
aldehydes in the ratio 3:1. So, to prepare porphyrins
1
4
–6 we started these studies by mixing pyrrol with
-pyridinecarboxaldehyde and dodecanal at 140 °C, in
the presence of a mixture of acetic acid/nitrobenzene as
solvent/oxidizer [20, 21].
After one hour, the reaction was stopped and the
solvent removed by distillation. The statistical mixture of
porphyrins was then separated by preparative silica TLC
plates and the six statistical products isolated, where
Determination of melting point intervals was carried
out for all synthesized compounds, in order to establish a
direct comparison between size and polarity effects on the
melting points of the materials (Table 3). For compounds
synthesized from dodecanal and 4-carboxypiridine
aldehyde (1–6), from Table 3 it can be verified that when
four alkyl chains are present at meso-positions (1), a melting
point interval of 80–81 °C is observed. When one pyridyl
substituent is present in the molecule (2), an associated
melting point increase to 83–85 °C is also observed, while
when the number of pyridyl substituents is increased to two,
A B type structural isomers are obtained and, as expected,
3
2
5
.9%, 3.5% and 2.0% yields were obtained for porphyrins
, 3 and 4, respectively, as described in Table 1 (entries 3,
and 7), among the other products.
Thelowyieldsobtainedareattributedtothepoorreactivity
of alkyl aldehydes [29], and so the experience was repeated
but with a 4:1 ratio of dodecanal/4-pyridinecarboxaldehye.
After purification by the same method as above described,
it could be verified an increase in the yields (Table 1; entries
2
2
distinct physical properties, regarding the melting point
interval, arise. If the isomer is the one that possesses two
pyridyl groups at adjacent meso-positions, melting point
4, 6 and 8), which confirms the lower reactivity of alkyl
aldehydes, when compared to aryl ones.
Table 1. Preparation of porphyrins 1–6 by statistical condensation of dodecanal and 4-pyridinecarboxaldehyde with pyrrol, by the
nitrobenzene method
R1
pyrrol
NH
N
N
O
R
+
N
R2
R3
nitrobenzene
acetic acid
O
HN
R4
Entry
Porphyrin
Dodecanal/
R1
R2
R3
R4
Yield, %
4
-pyridinecarboxaldehyde
1
2
3:1
4:1
0.5
0.5
1
2
C H
C H
C H
C H
11 23
1
1
23
11 23
11 23
3
4
3:1
4:1
1.2
3.9
4-pyridyl
C H
C H
C H
11 23
1
1
23
11 23
4-pyridyl
C H
5
6
3:1
4:1
<0.01
3.5
3
4
5
4-pyridyl
4-pyridyl
4-pyridyl
C H
C H
11 23
1
1
23
7
8
3:1
4:1
0.5
2.0
4-pyridyl
4-pyridyl
C H
11 23
1
1
23
9
0
3:1
4:1
1.1
0.5
4-pyridyl
4-pyridyl
C H
11 23
1
1
1
1
2
3:1
4:1
0.2
<0.01
6
4-pyridyl
4-pyridyl
4-pyridyl
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294
C.A. HENRIQUES ET AL.
Table 2. Preparation of porphyrins 6–11 by statistical condensation of tetradecanal and 4-pyridinecarboxaldehyde with pyrrol, by
the nitrobenzene method
R1
pyrrol
NH
N
N
O
R
+
N
R2
R3
nitrobenzene
acetic acid
O
HN
R4
Entry
Porphyrin
Tetradecanal/
R1
R2
R3
R4
Yield, %
4
-pyridinecarboxaldehyde
1
2
3:1
4:1
0.4
0.3
7
8
9
C H
C H
C H
C H
13 27
1
3
27
13 27
13 27
3
4
3:1
4:1
1.3
5.8
4-pyridyl
4-pyridyl
4-pyridyl
4-pyridyl
C H
C H
C H
13 27
1
3
27
13 27
5
6
3:1
4:1
0.4
3.1
C H
4-pyridyl
C H
13 27
1
3
27
7
8
3:1
4:1
1.1
1.4
1
1
0
1
4-pyridyl
4-pyridyl
C H
C H
13 27
1
3
27
9
0
3:1
4:1
1.2
0.8
4-pyridyl
4-pyridyl
C H
13 27
1
1
1
1
2
3:1
4:1
0.1
<0.01
6
4-pyridyl
4-pyridyl
4-pyridyl
Table 3. Melting point values for the
studied porphyrins (1–11)
between melting points and alkyl substituents size, while
maintaining similar polarity, with exception for the cases
when three pyridyl groups are present (5 and 11). In this
case the pyridyl effect is more pronounced when the
single alkyl chain is longer.
Porphyrin
Melting point, °C
80–81 [12]
83–85
1
2
3
4
5
6
7
8
9
73–74
Octanol/waterpartitioncoefficientsandphotophysical
properties
153–155
227–228
> 300 [23]
72–74
The effect of the number of pyridyl groups and the
size of the alkyl side chains at the meso-positions of
porphyrin on the 1-octanol/water partition coefficients
of the porphyrins using minor modifications from the
shake-flask method [24, 25] was evaluated. The desired
porphyrin was dissolved in 1-octanol saturated with
phosphorous buffer (PBS). This solution was then added
to a PBS solution saturated with 1-octanol. The two-layer
mixture was vigorously stirred, centrifuged and the phases
were separated. An appropriate volume of each phase
was taken and diluted with ethanol. The fluorescence of
each ethanol/1-octanol and ethanol/PBS solution was
measured, and compared with a calibration curve to obtain
the concentration of the photosensitizer. The solutions
of the calibration curves were either ethanol/1-octanol
or ethanol-PBS, with precisely weighed amounts of
porphyrin. The absorption band at ca. 419 nm was excited,
and fluorescence was collected in the red region, under
the same instrumental conditions for both the calibration
curve and the samples. The partition coefficients were
calculated according to the ratio Coct/CPBS, where Coct and
75–77
72–73
1
1
0
1
141–143
249–251
occurs around 73–74 °C, while for the other (pyridyl groups
at opposed meso-positions), melting point interval takes
place at 153–155 °C, a much higher value. When three
pyridyl groups are present in the molecule, the melting point
has already an expectable value of 227–228 °C.
The same trend is observed for the series 7–11. Instead
of dodecanal, tetradecanal was used as alkyl aldehyde,
and the increase in the number of carbons in the aliphatic
meso chain induces, as expected, an average ~7 °C
melting point lowering in its corresponding related
compounds (Table 3). A similar occurrence can be
observed when the number of pyridyl groups present in
the molecule increases, clearly indicating a close relation
CPBS are the concentrations of the porphyrin in 1-octanol
and in PBS, respectively, and are presented in Table 4.
Copyright © 2012 World Scientific Publishing Company
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UNSYMMETRICAL PORPHYRINS: THE ROLE OF MESO-SUBSTITUENTS ON THEIR PHYSICAL PROPERTIES
295
Table 4. Photophysical parameters (octanol/water partition
coefficients and fluorescence values) of the studied meso-
substituted unsymmetrical porphyrins
amounts of alkylaldehyde and pyridylaldehyde (from 3:1
to 4:1) revealed to be crucial for increasing the amount
of AB porphyrin type, from less than 0.01% to 3.5%
3
Entry
Porphyrin
Log POW
Fluorescence,
for 5,15-di(4-pyridyl)-10,20-di(undecyl)porphyrin 3 and
from 1.3% to 5.8% in case of 5-(4-pyridyl)-10,15,20-
tri(tridecyl)porphyrin 8. With this methodology a wide
range of amphiphilic porphyrins was obtained, as it was
FF
1
2
3
4
5
6
7
8
9
1
2
—
0.120
0.091
0.088
0.082
0.073
0.110
0.090
0.087
0.079
0.074
1.95
1.72
1.65
1.42
—
easily demonstrated by their log K , with values from
ow
3
1
.42 to 2.15. Furthermore, the number and size of the
4
alkyl chain revealed to be also a good strategy to obtain
porphyrins with melting points below 100 °C.
Various studies concerning the development of new
materials based on these compounds are currently
underway,especiallyonthemodulationoftheamphiphilic
properties of this type of porphyrins.
5
7
8
2.15
1.94
1.92
1.73
9
10
11
Acknowledgments
1
0
The authors thank FCT and QREN/FEDER (COM-
PETE-Programa Operacional Factores de Compe-
titividade) and project PTDC/QUI-QUI/112913/2009 for
funding.
The values of log KOW determined for unsymmetrical
pyridyl porphyrins show that the number of pyridyl
fragments in the meso-positions of the porphyrin
induce a moderate change in the hydrophilicity of these
compounds, being possible to observe a trend in the log
KOW of these sensitizers, since the increase of the number
of pyridyl fragments in the meso-positions induces a
decrease in the log KOW (Table 4 entries 2–5). However,
the increase of two carbons atoms in the alkyl chain,
present at the meso-positions, induces an increase in
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