Synthesis, structural characterization and protonation/deprotonation of hydroxyl-substituted free-base tetraphenylporphyrins in nonaqueous media

Article abstract of DOI:10.1142/S1088424613500557

A series of hydroxyl-substituted free-base tetraphenylporphyrins was synthesized and characterized by UV-vis spectroscopy, ¹H NMR and mass spectrometry. The porphyrins are represented as (HOPh)_n(tBuPh) _4-nPH₂, w

Full text of DOI:10.1142/S1088424613500557

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2013; 17: 1–13
DOI: 10.1142/S1088424613500557
Published at http://www.worldscinet.com/jpp/
Synthesis, structural characterization and protonation/
deprotonation of hydroxyl-substituted free-base
tetraphenylporphyrins in nonaqueous media
a◊◊
a
a
b
a
a
Guifen Lu , Xiufeng Zhang , Xu Cai , Yuanyuan Fang , Min Zhu , Weihua Zhu ,
a◊
b◊
Zhongping Ou* and Karl M. Kadish*
a
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, P. R. China
Department of Chemistry, University of Houston, Houston, TX 77204-5003, USA
b
Dedicated to Professor Vefa Ahsen on the occasion of his 60th birthday
Received 18 March 2013
Accepted 11 April 2013
ABSTRACT: A series of hydroxyl-substituted free-base tetraphenylporphyrins was synthesized
1
and characterized by UV-vis spectroscopy, H NMR and mass spectrometry. The porphyrins are
represented as (HOPh) (tBuPh) PH , where Ph presents a phenyl group, HO and tBu are substituents
n
4-n
2
on the para-positions of the phenyl rings of the macrocycle, n = 0–4 and P represents the dianion of
tetraphenylporphyrin. The UV-visible properties of each porphyrin were examined in dichloromethane
(
DCM), N,N′-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) before and after addition of
trifluoroacetic acid (TFA) or sodium hydroxide (NaOH) to solution. Equilibrium constants for protonation
(
logb ) and deprotonation (logb′) of each compound were determined using standard equations. The
n
n
protonations occur in a single step involving a simultaneous two proton addition at the porphyrin central
nitrogens. The phenolic protons on (HOPh) (tBuPh) PH are easier to deprotonate than the core nitrogen
n
4-n
2
protons of the porphyrins and this reaction occurs in a single step involving the simultaneous loss of 1–4
protons on the hydroxyl groups followed by a loss of two protons from the central nitrogens. The effect
of HO substituents on UV-visible spectra and the magnitude of the protonation/deprotonation constants
(
logb and logb′) are discussed. Two of the porphyrins, (tBuPh) PH and trans-(HOPh) (tBuPh) PH , are
n
n
4
2
2
2
2
also characterized by a single-crystal X-ray analysis.
KEYWORDS: hydroxyl-substituted free-base porphyrins, UV-vis spectra, protonation and
deprotonation, crystal structures.
porphyrins can be protonated and deprotonated, either
INTRODUCTION
in aqueous or nonaqueous media [11–14]. The gain or
loss of protons on these molecules is accompanied by
substantial changes in their spectroscopic properties, thus
potentially making them either more or less effective in a
variety of applications [15–17].
Our recent research interest has focused in part on
protonated and deprotonated free-base porphyrins [18]
and corroles [19–21] containing different electron-
donating or electron-withdrawing substituents on the
macrocycle. In the present work, we have expanded upon
our work in this area to include a newly synthesized series
of phenol-substituted free-base tetraphenylporphyrins
Free-base porphyrins have attracted a great deal
of interest, in part because of their spectral and
electrochemical properties [1–6] and in part because these
compounds can be utilized in a variety of biomedical
applications [7–10]. It is well-known that free-base
◊
SPP full and ◊◊ student member in good standing
*
Correspondence to: Zhongping Ou, email: zpou2003@yahoo.
com, tel/fax: +86 511-8879-1800; Karl M. Kadish, email:
kkadish@uh.edu, tel: +1 (713)-743-2740, fax: +1 (713)-743-
2
745
Copyright © 2013 World Scientific Publishing Company

2
G. LU ET AL.
where the HO groups can act not only as strongly electron-
withdrawing substituents on the tetraphenylporphyrin
macrocycle, but can also be deprotonated in nonaqueous
media containing added acid. The investigated
compounds are shown in Chart 1 and are represented
as (HOPh) (tBuPh) PH , where Ph presents a phenyl
properties so far for these kinds of compounds, and this is
done in the present paper where the porphyrins in Chart 1
were examined as to their UV-visible spectral properties
in dichloromethane (DCM), N,N′-dimethylformamide
(DMF) and dimethyl sulfoxide (DMSO) before and after
addition of TFA and NaOH to solution.
n
4-n
2
group, HO and tBu are substituents on para-position of
the meso phenyl rings of the macrocycle, n = 0, 1, 2, 3,
and 4 and P is a dianion of tetraphenylporphyrin.
Examination of the spectral properties for phenol-
substituted free-base porphyrins has atracted more
interests because these compounds have potential
applications in the photodynamic therapy of cancer
Each protonated and deprotonated free-base porphyrin
was spectroscopically characterized and the progress of
the acid or base titrations was monitored by UV-visible
spectroscopy, enabling calculation of both protonation
and deprotonation constants using standard equations.
The UV-visible spectra and protonation/deprotonation
constants for the series of hydroxylated porphyrins are
discussed in terms of the specific nonaqueous solvent and
number of HO groups on the macrocycle.
[
22]. However, to our knowledge, there have been no
systematicexaminationofthespectroscopicandacid/base
tBu
OH
NH
N
N
NH
N
N
tBu
tBu
tBu
tBu
OH
OH
tBu
tBu
HO
tBu
tBu
OH
HN
HN
tBu
tBu
(
tBuPh) PH
1
(HOPh)(tBuPh)3PH2 2
4
2
OH
OH
NH
N
N
NH
N
N
HN
HN
tBu
OH
trans-(HOPh) (tBuPh) PH 4
2
cis-(HOPh) (tBuPh) PH
3
2
2
2
2
2
OH
OH
NH
N
N
NH
N
HN
N
HN
OH
HOPh) (tBuPh)PH
OH
(HOPh) PH2 6
(
5
3
2
4
Chart 1. Structures of the investigated free-base porphyrins
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 2–13

PROTONATION/DEPROTONATION OF HYDROXYL-SUBSTITUTED FREE-BASE PORPHYRINS
3
cis-(HOPh) (tBuPh) PH 3. Anal. calcd. (%) for
EXPERIMENTAL
2
2
2
C H N O : C, 82.29; H, 6.11; N, 7.38. Found (%): C,
5
2
46
4
2
1
8
-
2.05; H, 6.24; N, 7.26. H NMR (DMSO-d ): d, ppm
2.89 (s, 2H), 1.57 (s, 18H), 7.22 (d, 4H), 7.84 (d, 4H),
6
Materials and equipment
8
9
7
.02 (d, 4H), 8.14 (d, 4H), 8.82 (t, 4H), 8.88 (s, 4H) and
.96 (s, 2H). MALDI-TOF mass: m/z calcd. 759.0, found
59.7.
N,N′-dimethylformamide and dichloromethane were
distilled over P O and pyrrole was distilled over CaH
2
5
2
under vacuum prior to use. TFA (99+%) and DMSO
were purchased from Sigma-Aldrich Chemical Co. All
other chemicals are analytical grade and used as received.
Column chromatography was carried out on silica gel
(
HOPh) (tBuPh)PH 5. Anal. calcd. (%) for
3 2
C H N O : C, 80.20; H, 5.33; N, 7.79. Found (%): C,
8
48 38
4
3
1
0.09; H, 5.41; N, 7.68. H NMR (DMSO-d ): d, ppm
6
-2.89 (s, 2H), 1.58 (s, 9H), 7.22 (d, 6H), 7.86 (d, 2H),
(
Merck, Kieselgel 60, 70-230 mesh) with the given eluent.
8
9
7
.01 (d, 6H), 8.16 (d, 2H), 8.81 (d, 2H), 8.87 (s, 6H) and
.96 (s, 3H). MALDI-TOF mass: m/z calcd. 718.8, found
UV-visible spectra were measured with an Agilent
1
8
453 diode array spectrophotometer. H NMR spectrum
19.5.
was measured on a Bruker DPX 300 spectrometer
300 MHz) in CDCl and DMSO-d . MALDI-TOF mass
1
(HOPh) PH 6. H NMR (DMSO-d ): d, ppm -2.88
(
4
2
6
3
6
(s, 2H), 7.22 (d, 8H), 8.01 (d, 8H), 8.87 (s, 8H) and 9.96
spectrum was recorded on a Bruker BIFLEX III ultrahigh
resolution with a-cyano-4-hydroxycinnamic acid as mat-
rix. Elemental analysis was performed on an Elementar
Vavio El III.
(s, 4H). MALDI-TOF mass: m/z C H N O , calcd.
44 30
4
4
6
78.7, found 679.1.
trans-(HOPh) (tBuPh) PH 4. The yield of 4 was very
2
2
2
low (see Table 1) with theAlder–Longo synthetic method
22, 23] and a modified synthetic route of Lindsey and
coworkers [28] was followed. The synthetic procedure is
shown in Scheme 1 and described below.
[
Synthesis
The free-base porphyrins were prepared according
to methods described in the literature [23–25]. Freshly
distilled pyrrole (5.5 mL, 80 mmol) was added over a
period of 15 min to a solution of tert-butyl benzaldehyde,
Pyrrole (30 mL, 0.45 mol) and tert-butyl benzaldehyde
(2.5 mL, 0.015 mol) were mixed and degassed with N2
for 5 min. After addition of TFA (100 mL, 1.5 mmol),
4
-hydroxybenzaldehyde and propionic acid (200 mL)
the solution was stirred under N at room temperature
2
at 140 °C. The solution was then refluxed for 30 min,
cooled and left overnight at -5 °C, and then filtered at
reduced pressure to give a dark purple powder. The crude
porphyrins were eluted on a silica gel column using
methanol/chloroform as eluent. The amount of the main
reactants utilized (pyrrole, tert-butyl benzaldehyde and
for 5 min and then quenched with K CO . The reaction
2
3
mixture was filtered and eluted with acetic ester.
The filtrate was collected and the solvent removed
under vacuum to give a gray solid. Purification of the
crude product by column chromatography (silica gel,
petroleum:ether-acetic ester = 3:1) afforded a light gray
4
-hydroxybenzaldehyde) and the yield of each isolated
product, 5-(4-tert-butylphenyl)dipyrromethane (3.97 g,
1
porphyrin are shown in Table 1.
95%). H NMR (CDCl , ppm): 1.29 (s, 9H), 5.43 (s, 1H),
3
1
(
tBuPh) PH 1. H NMR (CDCl ): d, ppm -2.70 (s,
5.93 (m, 2H), 6.16 (t, 2H), 6.67 (m, 2H), 7.14 (d, 2H),
7.33 (d, 2H), 7.87 (s, br, 2H).
4
2
3
2
H), 1.64 (s, 36H), 7.79 (d, 8H), 8.18 (d, 8H) and 8.90
(
s, 8H). MALDI-TOF mass: m/z C H N , calcd. 839.2,
A mixture of 5-(4-tert-butylphenyl)dipyrromethane
(2.78 g, 10 mmol), 4-hydroxybenzaldehyde (1.22 g,
10 mmol) and ammonium chloride (1.69 g, 30 mmol) in
DMSO (100 mL) was heated at 90 °C for 24 h and then
cooled to room temperature. The crude reaction mixture
was filtered and the solid then purified by column
6
0
62
4
found 840.7.
1
(
HOPh)(tBuPh) PH 2. H NMR (CDCl ): d, ppm
3
2
3
-
8
2.71 (s, 2H), 1.64 (s, 9H), 7.12 (d, 2H), 7.78 (d, 6H),
.07 (d, 2H), 8.18 (d, 6H) and 8.88 (t, 8H). MALDI-TOF
mass: m/z C H N O, calcd. 799.1, found 800.7.
5
6
54
4
Table 1. Amount of the main reactants (mmol) and yield (%) of the free-base porphyrins
Compound
Pyrrole, mmol
tert-butyl
4-hydroxy
Yield, %
benzaldehyde, mmol benzaldehyde, mmol
(
tBuPh) PH 1
80
80
80
80
80
80
80
20
40
40
60
0
0
40
30
15
0.2
10
7
4
2
(
HOPh)(tBuPh) PH 2
60
40
40
20
80
3
2
cis-(HOPh) (tBuPh) PH 3
2
2
2
trans-(HOPh) (tBuPh) PH 4
2
2
2
(
(
HOPh) (tBuPh)PH 5
3
2
HOPh) PH 6
4
2
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 3–13

4
G. LU ET AL.
1
. TFA
+
N
H
2. K CO
2
3
CHO
NH HN
OH
OH
DMSO/NH4Cl
0 °C
NH
N
+
9
N
NH
CHO
NH HN
OH
Scheme 1. Synthesis route for the preparation of trans-(HOPh) (tBuPh) PH 4
2
2
2
chromatography (silica gel, chloroform). After removal
of the solvent and drying under vacuum the purple solid
of trans-(HOPh) (tBuPh) PH 4 was obtained. Yield 5%.
cell. After each addition of acid or base, the solution
was thoroughly mixed and the spectrum recorded. The
changes in spectra were analyzed as a function of the
concentration of added acid or added base and the Hill
equation was used to calculate the equilibrium constants,
logb and logb′, as described in the literature [19, 20,
2
2
2
Anal. calcd. (%) for C H N O : C, 82.29; H, 6.11; N,
5
2
46
4
2
7
.38. Found (%): C, 82.39; H, 6.12; N, 6.96. MALDI-
1
TOF mass: m/z calcd. 759.0, found 759.1. H NMR
n
n
(
(
(
DMSO-d ): d, ppm -2.90 (s, 2H), 1.59 (s, 18H), 8.17
d, 4H), 8.01 (d, 4H), 7.87 (d, 4H), 7.22 (d, 4H), 8.89
d, 4H), 8.82 (d, 4H) and 9.96 (s, 2H).
26, 27]. Equilibrium constants were measured at room
temperature (298 K).
6
X-ray crystallography
RESULTS AND DISCUSSION
Single crystals of (tBuPh) PH
1 and trans-
4
2
(
HOPh) (tBuPh) PH 4 for X-ray diffraction analysis
Synthesis and characterization
2
2
2
were obtained by slow diffusion of methanol into toluene
and chloroform solutions, respectively. The crystals were
mountedonaglassfiberandthecrystaldatawerecollected
on a Bruker SMART APEXII CCD diffractometer with
graphite monochromatic Mo Ka radiation (l = 0.71073Å)
using a w scan mode at 293 K. The crystal structure was
solved by direct methods (SHELXS-97) and refined
The investigated porphyrins possessed zero, one,
two, three and four hydroxyl substituents on the para-
positions of the meso-phenyl rings and tert-butyl groups
at the para-positions lacking an HO group. The use
of tert-butyl phenyl groups was to give the porphyrins
increased solubility in common organic solvents such as
chloroform, DCM and DMF. The difference in polarity
between the tert-butyl and hydroxyl substituents on the
compounds also enabled the hydroxylated porphyrins in
the series to be more easily separated and purified.
As seen in Table 1, a relative good yield was obtained
for compounds 1–3, 5 and 6 when the Alder–Longo
method was utilized. However, this was not the case for
compound 4, where the yield was only 0.2% by the same
method. This compound was therefore synthesized by
condensation of 5-(4-tert-butylphenyl)-dipyrromethane
2
by fullmatrix least-squares (SHELXL-97) on F . The
non-hydrogen atoms were refined anisotropically and
hydrogen atoms were added according to theoretical
models. Intensity data were corrected for factors and
empirical absorption.
Determination of equilibrium constants
A series of TFA/DCM, TFA/DMF or TFA/DMSO
mixed solvents containing different concentrations of
TFA was prepared and used as the acid-titration reagent.
and 4-hydroxybenzaldehyde in the presence of an NH Cl
4
-6
The base-titration reagent was NaOH solution (1.2 × 10
1.2 M). In order to study the spectral changes in situ,
catalyst [28] and was obtained with a higher yield of 5%.
The MALDI-TOF mass spectrum of each compound
clearly shows an intense signal for the molecular ion
-
micro-liter quantities of the above standard solutions
were added gradually to a 5.5 mL DCM, DMF or
DMSO solution of the porphyrin in a home-made 1.0 cm
+
1
[M] . Well-resolved H NMR spectra are observed in
DMSO-d
and the peak assignments could easily be
6
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 4–13

PROTONATION/DEPROTONATION OF HYDROXYL-SUBSTITUTED FREE-BASE PORPHYRINS
5
reached on the basis of integration and multiplicity of the
signals.
atom and porphyrin core, giving a three-dimensional
supramolecular packing mode. However, there are two
methanol molecules in the crystal structure of 4 and the
neighboring molecules in 4 are connected by hydrogen
bonds. As seen in Fig. 2, methanol molecules are located
in the cavity of the crystals and are involved in hydrogen
bondingwithinthesuperstructure;thisdiffersfromwhatwas
observed for 5,10,15,20-tetrakis(3,5-dimethyl-4-hydroxy-
phenyl)porphyrin [29].
X-ray single crystal structure
The crystal and molecular structures of (tBuPh) PH
4
2
1
and trans-(HOPh) (tBuPh) PH 4 were determined
2 2 2
by X-ray diffraction analyses. The crystal data are
summarized in Table 2 and the molecular structures are
shown in Fig. 1. Both compounds 1 and 4 crystallize in
the monoclinic system with P21/c space group.
Compounds 1 and 4 have four identical substituents
on the meso-positions of the porphyrin macrocycle and
exhibit C2v asymmetry. The four meso-phenyl rings are
neither parallel nor perpendicular with the conjugated
porphyrin p system and the dihedral angles between
the phenyl substituent and the porphyrin mean plane are
There are two kinds of H-bonding in this network.
One is between the imine nitrogen (N ) and methanol
1
_
…..
hydrogen (H ) [O H N = 2.948(4) Å, ∠O H N =
3
3
3
1:
3
3
1
o
1
67.5 , symmetry code: x, -y + 1/2, z + 1/2]. The other
is between the phenolic hydrogen (H ) and the methanol
1
_
…..
oxygen (O ) [O H O : = 2.693(3) Å, ∠O H O =
72.4 , symmetry code: -x + 2, -y, -z + 1]. The cooperation
3
1
1
3
1
1
3
o
1
between these two kinds of hydrogen bonding leads to
a comparatively complicated three-dimensional supra-
molecular structure (Fig. S1).
6
1.8 and 70.4° for 1 and 62.3 and 80.6° for 4 due to the
steric effect. It is worth noting that crystal packing of the
porphyrin molecules in 1 and 4 are different from each
other because of the different peripheral substituents and
solvent molecules in the crystal.
UV-vis spectral properties
For compound 1, the neighboring molecules exhibit
intermolecular C-H p bonds between the phenyl hydrogen
Previouslycharacterized4-hydroxyphenylsubstituents
free-base porphyrins were shown to exhibit a single sharp
...
Table 2. Crystallographic data for (tBuPh) PH (1) and trans-(HOPh) (tBuPh) PH (4)
4
2
2
2
2
1
4
Empirical formula
Formula weight
Crystal size, mm
Crystal system
Space group
a, Å
C H N
C H N O
54 54 4 4
6
0
62
4
839.14
823.01
0.23 × 0.22 × 0.19
0.22 × 0.20 × 0.20
monoclinic
monoclinic
P2 /c
P2 /c
1
1
13.637(3)
16.274(3)
11.482(2)
2450.3(8)
2
12.461(3)
15.818(3)
12.572(3)
2286.92
2
b, Å
c, Å
3
Volume, A
Z
F (000)
900
876
3
Calculated density, mg/m
1.137
1.195
-
1
Absorption coefficient, mm
0.066
0.075
o
q range ( ) for data collection
3.11–25.33
3.12–25.34
-
13 ≤ h ≤ 16,
-19 ≤ k ≤ 15,
12 ≤ l ≤ 13
-15 ≤ h ≤ 11,
-15 ≤ k ≤ 19,
-12 ≤ l ≤ 15
Limiting indices
-
Reflections collected
11351
11513
Unique reflections [R(int)]
Completeness to q = 25.34 (%)
Final R indices [I > 2(I)]
4439 [R(int) = 0.0581]
4134 [R(int) = 0.0524]
99.1%
99.1%
R1 = 0.0820, wR2 = 0.1698 R1 = 0.0826, wR2 = 0.2634
2
goodness of fit (GOF) on F
1.004
1.039
-
3
Largest diff. in peak and hole, e.A
0.488 and -0.551
0.411 and -0.247
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 5–13

6
G. LU ET AL.
Fig. 2. Hydrogen-bonding manifold in trans-(HOPh) (tBuPh) -
2
2
PH 4 involves all of its phenolic protons, the core nitrogen
2
atoms and the methanol molecules. Important bond lengths and
angles: O1-O3, 2.693(3) Å; O3-N1, 2.948(4) Å; ∠O1-H1-O3,
1
72.4°; ∠O3-H3-N1, 167.5°
regardless of the number and position of the hydroxyl
groups. This is not the case in DMF and DMSO where
the Soret and Q-bands dependent upon the number of
HO groups and type of solvent as discussed later in the
manuscript.
+
-
The addition of H or OH to solutions of free-base
porphyrins has been shown to result in significantly
different UV-visible spectra [11–17]. This is also the
case for the currently studied compounds. For example,
in DMSO, neutral (HOPh) (tBuPh)PH 5 has a Soret
3
2
band at 424 nm and four Q-bands at 520, 557, 599 and
56 nm (Table 3). However, for the same compound in
6
Fig. 1. Molecular structures of (a) (tBuPh) PH 1 and (b) trans-
solutions of DMSO with added TFA, the Soret band is
red-shifted to 458 nm and only one Q-band is observed
at 702 nm. This change of the spectral properties is
consistent with protonation of the porphyrin nitrogens
under the given solution conditions. Different spectra are
also seen for the deprotonated porphyrins as shown Fig. 3
which illustrated the UV-vis spectrum of compound 5
in its neutral, protonated and deprotonated forms. The
4
2
(
HOPh) (tBuPh) PH 4 (showing 30% probability thermal
2 2 2
displacement ellipsoids)
Soret band and four Q-bands between 510 and 650 nm
[
30] and this is also the case for compounds 1–6 in DCM,
DMF and DMSO. The spectra of each porphyrin in DCM
Table 3) are similar to each other in a given solvent,
(
Table 3. UV-visible spectral data (lmax, nm) in DCM, DMF and DMSO
Compound In DCM
Q-bands
In DMF
Q-bands
In DMSO
Q-bands
Soret band
Soret band
Soret band
(
tBuPh) PH 1
420
420
420
420
420
a
517, 553, 592, 645
518, 554, 592, 645
518, 553, 594, 647
518, 553, 594, 649
519, 554, 594, 651
a
419
420
421
421
422
423
517, 551, 595, 631
517, 554, 594, 640
517, 556, 594, 643
516, 556, 596, 650
520, 557, 595, 652
519, 558, 597, 652
a
a
4
2
(
HOPh)(tBuPh) PH 2
422
423
423
424
425
519, 556, 597, 651
517, 553, 598, 652
519, 555, 598, 650
520, 557, 599, 656
521, 560, 597, 655
3
2
cis-(HOPh) (tBuPh) PH 3
2
2
2
trans-(HOPh) (tBuPh) PH 4
2
2
2
(
HOPh) (tBuPh)PH 5
3
2
(
HOPh) PH 6
4
2
a
No data obtained due to the very limited solubility of the compound under the given solution conditions.
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 6–13

PROTONATION/DEPROTONATION OF HYDROXYL-SUBSTITUTED FREE-BASE PORPHYRINS
7
2
0, 26, 27]. The diagnostic plot for analysis
of the data at 415 nm is shown as an insert in
Fig. 4 where a linear relationship is seen in
the plot of log[(A -A )/(A -A )] vs. log[TFA].
i
o
f
i
The slope of the line is 2.0, indicating that
two protons are added in a one-step process
2
+
to give [(HOPh)(tBuPh) PH ] as the final
3
4
protonation product. A protonation constant
of logb = 4.7 was then calculated from the
2
zero intercept of the plot.
Similar changes in the UV-vis spectra
were observed for the five other porphyrins
when TFA was stepwise added to a DMF
solution of the compound (Fig. S2). In each
case the final products of titration exhibited a
red shifted Soret band and a single Q-band at
Fig. 3. UV-vis spectra of the neutral, protonated and deprotonated HO or NH
forms of (HOPh) (tBuPh)PH 5 in DMSO
673–710 nm. These types of spectral changes
3
2
are typical for formation of a diprotonated
porphyrinin nonaqueous media [11, 31].
protonation and deprotonation reactions are discussed in
the following sections of the manuscript.
The protonation reactions of compounds 1–6 was also
investigated in DCM and DMSO and in each solvent
two protons were again added in a single step (n = 2.0).
Protonation reactions
Values of logb are given in Table 4 and ranged from 9.4
2
to 9.9 in DCM, from 3.3–5.4 in DMF and from 3.5–4.6
in DMSO, respectively.
Figure 4 illustrates the UV-vis changes of (HOPh)
(
tBuPh) PH 2 during a titration with TFA in DMF. As
3 2
seen in this figure, the Soret band of the neutral porphyrin
at 420 nm decreases in intensity while a new Soret band
at 451 nm grows in for the diprotonated porphyrin. The
number of Q-bands is also reduced from four (at 517, 554,
Deprotonation reactions
The deprotonation reactions of 1–6 were examined by
titration with NaOH in DMF and DMSO during addition
of NaOH into solutions of the compound. Examples of
the spectral changes are given in Figs 5–7 and a summary
of the data is given in Table 5.
5
94 and 640 nm) to one (at 684 nm) as the protonated
porphyrin is generated according to Equation 1.
+
(
HOPh)(tBuPh) PH + 2H
3 2
Compound 1 contains no hydroxyl groups and only the
central NH groups of (tBuPh) PH can be deprotonated.
2
+
ꢀ
[(HOPh)(tBuPh) PH ]
(1)
3
4
4 2
This reaction occurs in a single step with a loss of two
protons as indicated by the slope of the Hill plot (n =
2.0) in Fig. 5. This result is consistent with results
previously reported for the structurally related porphyrins
[(OCH ) Ph] PH [31] and (Ph) PH [32]. The prevailing
The spectral changes in Fig. 4 were analyzed as
a function of the TFA concentration which enabled
calculation of the number of protons added and the
protonation constant (logb ) using the Hill equation [19,
n
3 3
4
2
4
2
Fig. 4. UV-visible spectral changes of (HOPh)(tBuPh) PH 2 in DMF during protonation of the central nitrogens by addition of TFA
3
2
to solution. The insert shows the Hill plot used for calculation of the logb2
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 7–13

8
G. LU ET AL.
Table 4. UV-vis spectral data (lmax, nm) of protonated free-base porphyrins and the protonation constants (logb ) in DCM, DMF
2
and DMSO
Compound
In DCM
In DMF
In DMSO
Soret band Q-band
n
logb2 Soret band Q-band
n
logb2 Soret band Q-band
n
logb2
(
tBuPh) PH 1
445
445
445
445
447
a
670 2.0 9.9
672 2.0 9.7
675 2.0 9.6
675 2.0 9.6
680 2.0 9.4
447
451
453
454
455
456
673 2.0 3.3
684 2.0 4.7
690 2.0 4.8
692 2.0 5.1
699 2.0 5.2
710 2.1 5.4
a
a
a
a
4
2
(
HOPh)(tBuPh) PH 2
451
454
456
458
458
692 2.0 3.5
696 2.0 3.8
697 2.0 4.0
702 2.0 4.4
711 2.0 4.6
3
2
cis-(HOPh) (tBuPh) PH 3
2
2
2
trans-(HOPh) (tBuPh) PH 4
2
2
2
(
HOPh) (tBuPh)PH 5
3
2
(
HOPh) PH 6
a
a
a
4
2
a
No data obtained due to the very limited solubility of the compound under the given solution conditions.
Fig. 5. UV-visible spectral changes of (tBuPh) PH 1 during deprotonation by addition of NaOH in DMF
4
2
Table 5. Equilibrium constants (logb′ and logb″) for HO- and NH-deprotonation reactions of the free-base porphyrins in DMF and
n
2
DMSO
Compound
In DMF
In DMSO
HO-deprotonation NH-deprotonation
HO-deprotonation
NH-deprotonation
#
#
n
logbn′ logb′/ HO
n
logb2″
n
logbn′ logb′/ HO
n
logb2″
n
n
(
tBuPh) PH 1
—
1.0
2.0
—
3.9
—
3.9
2.0
2.0
2.0
2.0
2.0
2.0
7.0
6.7
5.9
5.3
5.1
5.0
—
1.0
2.0
2.0
3.0
4.0
—
4.4
—
4.4
a
a
4
2
(
HOPh)(tBuPh) PH 2
2.0
2.0
2.0
2.0
2.0
7.9
7.1
6.8
6.2
6.1
3
2
cis-(HOPh) (tBuPh) PH 3
7.0
3.5
9.0
4.5
2
2
2
trans-(HOPh) (tBuPh) PH 4 2.0
7.7
3.85
9.4
4.7
2
2
2
(
(
HOPh) (tBuPh)PH 5
3.0
4.0
10.6
13.3
3.52
13.6
17.3
4.52
3
2
HOPh) PH 6
3.32
4.32
4
2
Average value of logb′
3.62 ± 0.25
4.49 ± 0.14
a
No data obtained due to the low solubility of the compound under the given solution conditions.
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 8–13

PROTONATION/DEPROTONATION OF HYDROXYL-SUBSTITUTED FREE-BASE PORPHYRINS
9
reaction is shown in Equation 2 and the calculated value
of logb″ = 7.0.
the titration of a same compound. The spectral changes
of compound 6 were also similar to that of previously
reported in the literature [32] for the same compound. The
Hill plots show a slope of 1.0 to 4.0 for the first step of the
deprotonation where the experimentally observed value
of n corresponds to the number of phenol HO groups on
the porphyrin. The slope of the Hill plot in the second
step ranges from 2.0 to 2.1 and involves deprotonation of
the central nitrogen protons. This result indicates that all
of the phenol groups on 2–6 are initially deprotonated in
a simultaneous process involving 1–4 non-interacting HO
2
-
2-
(
tBuPh) PH + 2OH ꢀ [(tBuPh) P] + 2H O (2)
4 2 4 2
In contrast to compound 1, two sets of well-defined
spectral changes were obtained during the titration of 2–6
with NaOH in DMF and DMSO.As examples the spectral
changes of these compounds during the base titration
were illustrated in Figs 6 and 7. Similar spectral changes
were seen when the DMF was utilized as a solvent during
Fig. 6. UV-visible spectral changes during (a) HO-deprotonation and (b) NH-deprotonation of the phenol substituted free-base
porphyrins 2–5 by addition of NaOH in DMSO. The inset shows the Hill plots used for calculation of the logb′n
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 9–13

1
0
G. LU ET AL.
Fig. 7. UV-visible spectral changes of (HOPh) PH 6 in DMSO during (a) the first and (b) second protonation steps with addition of
4
2
NaOH solutions. The insert shows the Hill plot used for calculation of the logb′ and logb″
4
2
substituents followed by a simultaneous deprotonation of
the two central NH protons as shown in Equations 3 and
from zero to four has no effect on the UV-visible spectra
in this solvent. The phenyl HO groups are expected to
hydrogen bond with the DMSO and DMF solvents and
this solvent-porphyrin interaction would be increased as
the number of HO groups on the molecule increases from
1 to 4. In contrast, little to no solvent interaction would
be expected between DCM solvent and the phenol HO
groups. Under these conditions, almost the same UV-vis
spectrum might be expected for the six investigated
compounds in this solvent, and this is indeed the case.
4
as well as Scheme 2.
-
(
HOPh) (tBuPh) PH + nOH
n
4-n
2
ꢀ
[(OPh) (tBuPh) PH2 ]n- + nH O
(3)
n
4-n
n-
2
-
[
(OPh) (tBuPh) PH2 ] + 2OH
n
4-n
[(OPh) (tBuPh) P](n+2)- +(n+ 2)H O (4)
ꢀ
n 4-n 2
Effect of HO substituents on the neutral spectra
Effect of HO substituents on protonation/
deprotonation reactions
Figure 8 plots the energy of the Soret band (E) for
the investigated porphyrins in DCM, DMF or DMSO
vs. the number of HO groups on the meso-phenyl rings
of the macrocycle. A linear relationship is seen in DMF
and DMSO where the energy systematically shifts
towards lower values with increase of the number, but
not the position of the phenol substituents. The fact that
almost identical UV-visible spectra are obtained for cis-
Shown in Fig. 9 are plots of the measured protonation
reaction constants (logb ) in DCM, DMF and DMSO vs.
2
the number of HO groups on the porphyrin. As seen from
this figure, the value of logb for protonation at the central
2
nitrogens of the porphyrins gradually increases upon
going from compound 1 to 6 in both DMF and DMSO
but a different trend is again observed in DCM, where
(
HOPh) (tBuPh) PH 3 and trans-(HOPh) (tBuPh) PH 4
logb decreases slightly with increase in the number of
2
2
2
2
2
2
2
in all three solvents (see lmax values in Table 3), indicates
that the position of the two phenol substituents has no
effect on the spectral properties of these compounds. The
linear relationship between the number of HO substituents
on the compounds and the energy of the porphyrin Soret
band in DMSO and DMF contrasts with what occurs in
DCM where increasing the number of phenol substituents
HO groups. Based only on the fact that HO is an electron-
donating substituent [33] one might expect an increase
in logb in all three solvents but this is not observed and,
2
in fact, the substituent effect of the added HO groups on
logb is close to negligible.
2
Plots of the measured deprotonation constants for the
1–4 protons of the phenol groups and the two protons
Copyright © 2013 World Scientific Publishing Company
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PROTONATION/DEPROTONATION OF HYDROXYL-SUBSTITUTED FREE-BASE PORPHYRINS
11
N-
N-
N
H
>
-2H+
>
cpd 1
>N
N
>N
N
H
N
logβ2''
neutral porphyrin
HO-deprotonated
NH-deprotonated
HO
N
O-
O-
N-
>
N
-2H+
>
-H+
>
H
H
cpd 2
cpd 3
>N
N
N
>N
N
>N
N
H
N
logβ1'
H
N
logβ2''
N-
O-
O-
O-
O-
HO
OH
N-
N-
N
H
N
H
-2H+
-2H+
>
>
>
>N
>N
N
>N
N
logβ2'
logβ2''
H
N
H
N
O-
O-
HO
N-
N-
N
H
N
-2H+
-2H+
>
>
>
>
H
cpd 4
>N
N
>N
N
>N
N
logβ2'
logβ2''
H
N
H
N
O-
O-
O-
OH
OH
O-
O-
O-
HO
N-
N-
N
H
N
H
-3H+
-2H+
>
>
cpd 5
cpd 6
>N
N
>N
N
>N
N
logβ3'
logβ2''
H
N
H
N
O-
O-
O-
O-
OH
OH
O-
O-
HO
HO
N-
N-
N
H
N
H
>
4H+
>
-2H+
>
-
>
N
N
N
N
>N
N
>
H
N
logβ4'
logβ2''
H
N
OH
O-
O-
O-
O-
Scheme 2. Deprotonation reaction mechanisms of the porphyrins in DMF and DMSO with added NaOH solutions
Fig. 8. Plots of the energy (eV) of the Soret band vs. the
number of hydroxyl groups on the four meso phenyl rings of
the porphyrin macrocycle. The values of lmax for the Soret band
of each compound is given in Table 3
Fig. 9. Plots of the protonation reaction constants (logb ) vs. the
2
number of hydroxyl groups on the four meso phenyl rings of the
porphyrin macrocycle
Copyright © 2013 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2013; 17: 11–13

1
2
G. LU ET AL.
derivative while compound 6 contains four negative
charges after deprotonation of all four phenol protons
4
-
and formation of [(OPh) PH ] .
4
2
CONCLUSION
In summary, we have synthesized a series of meso
phenol substituted free-base porphyrins and determined
the protonation and deprotonation constants of these
compounds in three nonaqueous solvents. Each free-
base porphyrin was doubly protonated in a single step
by addition of TFA, leading to formation of [(HOPh) -
n
2
+
(
tBuPh) PH ] in all three solvents. The meso-phenol
4-n 4
and central nitrogen protons of the free-base porphyrins
were also deprotonated by titration with NaOH in DMF
and DMSO solutions. The meso-phenol protons are
easier to deprotonate than the two protons at the central
nitrogen atoms of the porphyrin and deprotonation of the
hydroxyl group occurs as the first step in a titration of the
porphyrin with NaOH.
Fig. 10. Plots of the HO- and NH-deprotonation constants
(
logb′ and logb″) vs. the number of hydroxyl groups on the
Acknowledgements
n
2
four phenyl rings of the macrocycle
We gratefully acknowledge supports from the
Natural Science Foundation of China (No. 21071067,
2
1001054), Postdoctoral Science Foundation of China
of the porphyrin central nitrogens in compounds 2–6 are
illustrated in Fig. 10. In order to better understand the
trend in logb′ for deprotonation of the phenol protons
on (HOPh) (tBuPh) PH , we have plotted in Fig. 10a
(2012M511203) and Jiangsu Province (1102126C), and
the Robert A. Welch Foundation (K.M.K., Grant E-680).
n
4-n
2
Supporting information
the magnitude of logb′ divided by the number of HO
#
groups. This value is given in Table 5 as logb′/ HO
Stereoview of the interlinked supramolecular organiz-
ation for compound 4 and UV-visible spectral changes
during protonation of free-base porphyrins 1, 3–6 by
addition of TFA in DMF (Figs S1 and S2) are given in
the supplementary material. This material is available
free of charge via the Internet at http://www.worldscinet.
com/jpp/jpp.shtml.
Crystallographic data for 1 and 4 have been deposited
at the Cambridge Crystallographic Data Centre (CCDC)
under numbers CCDC-829498 and 827924. Copies
can be obtained on request, free of charge, via www.
ccdc.cam.ac.uk/data_request/cif or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44 1223-336-033 or email: deposit@
ccdc.cam.ac.uk).
and is justified on the basis of the fact that all of the
phenol deprotonations occur in a single overlapping
step involving 1–4 HO groups depending on the specific
compound. Under these conditions, all of the hydroxyl
porphyrins have the same individual logb′ values. When
examing the average deprotonation constants for 2–6 it
can be seen that the logb′ values for deprotonation of the
phenol HO groups are higher in DMSO than in DMF, and
in both solvents, there is a slight decrease of logb′ with
increase in the number of HO groups. The average logb′
for the five hydroxylated porphyrins is 3.62 in DMF and
4
.48 in DMSO (Table 5).
Similar to what is observed for deprotonation of
the phenol protons, the values of logb″ for the NH-
2
deprotonation also decrease with increasing number
of phenol groups on the compound. Again the
experimentally measured values are higher in DMSO
than in DMF (see Fig. 10b). For example, the measured
logb″ decreases from 7.9 for (HOPh)(tBuPh) PH 2 to
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