Synthesis, spectral, structural and antimicrobial studies of fluorinated porphyrins

Article abstract of DOI:10.1016/j.poly.2015.05.018

Abstract We have reported the synthesis, spectral and anti-microbial studies of 5,10,15,20-tetrakis(4′-trifluoromethylphenyl)porphyrin derivatives, MT(4′-CF₃P)Ps where M = 2H, 1; Fe(II), 2; Ni(II), 3; Cu(II), 4; Zn(II), 5 and Pt(II), 6. The opt

Full text of DOI:10.1016/j.poly.2015.05.018

Accepted Manuscript
Synthesis, spectral, structural and antimicrobial studies of fluorinated porphyr-
ins
Fasalu Rahman Kooriyaden, Subramaniam Sujatha, Chellaiah Arunkumar
PII:
S0277-5387(15)00260-0
DOI:
http://dx.doi.org/10.1016/j.poly.2015.05.018
POLY 11317
Reference:
Polyhedron
To appear in:
Received Date:
Accepted Date:
13 January 2015
1 May 2015
Please cite this article as: F.R. Kooriyaden, S. Sujatha, C. Arunkumar, Synthesis, spectral, structural and
antimicrobial studies of fluorinated porphyrins, Polyhedron (2015), doi: http://dx.doi.org/10.1016/j.poly.
2015.05.018
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Synthesis, spectral, structural and antimicrobial studies of fluorinated
porphyrins
Fasalu Rahman Kooriyaden†, Subramaniam Sujatha† and Chellaiah Arunkumar*
Bioinorganic Materials Research Laboratory, Department of Chemistry, National Institute of Technology
Calicut, Kozhikode, Kerala, India - 673 601
Abstract:
______________________________________________________________________________
We have reported the synthesis, spectral and anti-microbial studies of 5,10,15,20-tetrakis(4
trifluoromethylphenyl)porphyrin derivatives, MT(4 -CF3P)Ps where M = 2H, ; Fe(II),
Ni(II), ; Cu(II), ; Zn(II), and Pt(II), . The optical absorption and steady state
fluorescence spectra of show characteristic bands comparable with MTPPs. Compounds
and were structurally characterized using single crystal X-ray diffraction analysis;
and crystallized in the triclinic system, whereas and in the monoclinic system. The
high spin nickel(II) ion in is well placed at the centre of the planar porphyrin core, which
is influenced by the presence of trifluoromethylphenyl groups at the periphery and two THF
molecules in apex positions. The porphyrins and are arranged in a slip-stacked fashion
involving C H··· and C F···H(sol) intermolecular close contacts for and
′-
′
1
2;
3
4
5
6
1-6
1
3
-5
1
4
3
5
3
1
3-5
−
π
−
1
,
4
3, 5
respectively. The role of non-covalent interactions involving the trifluoromethylphenyl
groups in the crystal packing have been analyzed and quantified using Hirshfeld surface
analysis. The antimicrobial activity of the free ligand is higher compared to its metal
complexes.
Keywords: Trifluoromethylphenyl porphyrin, Photophysical properties, Crystal structure
analysis, Non-covalent interactions, Hirshfeld surface analysis, Antimicrobial studies.
________________________________________________________________________
*
Corresponding author. Fax: 0495-2287250; E-mail address: arunkumarc@nitc.ac.in (C. Arunkumar)
†Equally contributed to this work.
1

Introduction
Porphyrinoids have been widely studied due to their spectroscopic, electrochemical and
luminescent properties and their novel biological activities. Synthetic porphyrin analogues
closely resemble naturally occurring tetrapyrrole macrocycles and hence they are considered to
be the appropriate ligands of choice for mimicking the natural processes [1]. The introduction of
suitable substituents at the peripheral positions of the porphyrin periphery provokes tunable
shape, size and symmetry and are found in material [2] and therapeutic applications [3,4]. It is
well known that the pharmacological properties of organic molecules can be enhanced by the
incorporation of fluorine atoms which subsequently makes them more abundant in the market as
effective drugs. In particular, drugs containing trifluoromethylphenyl groups, such as Prozac,
Sensipar, Arava, Travatan etc, are innumerable which leads to the huge success of fluorine
containing drugs in medicinal chemistry [5,6]. It is essential to analyze the various
intermolecular interactions which control the structure-property relationship of the fluorinated
drugs in binding to enzyme active sites. Moreover, upon fluorination, the pharmaco-kinetic
properties of the molecules are pronounced which leads to better binding and hence the superior
biological activity [7].
Porphyrin derivatives are excellent materials in crystal engineering [8-10] and we are
interested in the design and engineering of fluorinated porphyrins in order to understand the role
of close contacts involving fluorine in the crystal packing. Although fluorine substituted
porphyrins and their analogues have been actively studied in the recent years [11-13], it is noted
that detailed investigations on the structure and photophysical properties of fluorinated
porphyrins are limited. In this line, we were stimulated to investigate the spectral and
quantitative crystal structure analysis of electron deficient fluorinated metalloporphyrins
containing trifluoromethylphenyl groups (Fig. 1) and the influence of such groups in the crystal
packing motif of the porphyrins using Hirshfeld surface analysis [14]. Also, the antimicrobial
properties of the free ligand and their metal complexes were examined with two gram-negative
and two gram-positive bacterial strains, and one fungal strain.
2

F3C
CF3
N
M
N
N
N
F3C
CF3
M = 2H, 1; Fe(II), 2; Ni(II), 3; Cu(II), 4;
Zn(II), 5 and Pt(II), 6
Fig. 1. Molecular structure of the porphyrins under study.
Experimental
Materials and methods
The chemicals employed for the synthesis and used in other processes were commercially
available reagents of analytical grade and were used without further purification unless otherwise
specified. The solvents used for the synthesis were purified using the available literature methods
[15]. Optical spectra were recorded at room temperature in CH2Cl2 using a Systronics double
beam 2202 spectrophotometer and 1H NMR spectra were taken in a Bruker Avance III 400 MHz
spectrometer. Mass spectra were recorded under ESI/HR-MS at 61,800 resolution using a
Thermo Scientific Exactive mass spectrometer (Thermo Fischer Scientific, Bremen, Germany).
Fluorescence spectra and quantum yield measurements were performed using a Perkin Elmer LS
55 luminescence spectrophotometer.
Synthesis of 5,10,15,20-tetrakis-(4
′-trifluoromethylphenyl)porphyrin, H2T(4′-CF3P)P and
the metal complexes MT(4′-CF3P)P; M = Fe(II), Ni(II), Cu(II), Zn(II) and Pt(II).
Pyrrole (0.5 mL, 7.2 mmol) and 4-(trifluoromethyl) benzaldehyde (1.0 mL, 7.2 mmol)
were taken in a 500 mL two necked round bottom flask containing 350 mL of CH2Cl2 and the
content was purged with N2 gas for 15 min. Then, the acid catalyst BF3·OEt2 (0.1 mL, 2.5 M)
was introduced and the solution was stirred at room temperature for 1 h under an inert
atmosphere, followed by the addition of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, DDQ (760
mg). The reaction mixture was further stirred for one more hour at room temperature in air, the
solvent was removed by a rotary evaporator, then purification by column chromatography using
3

silica and hexane/chloroform as the eluent afforded the free ligand 1 in 35 % yield (550 mg). The
zinc(II) and copper (II) complexes were synthesized in a chloroform/methanol mixture using the
corresponding metal acetate, and the yields were obtained as 92 and 94 % respectively. The
nickel(II) and iron(II) complexes were prepared in DMF using the metal chloride as the metal
ion carrier, and the yield was found to be 61 and 74 % respectively. The platinum(II) complex
[16] was prepared in benzonitrile using K2[PtCl6] as the metal ion carrier and the yield was found
to be 85 %. UV-Visible data of porphyrins in CH2Cl2, λmax (log ε/M−1 cm−1): 1, 417 (5.81), 512
(4.59), 552 (4.21), 588 (4.20), 645 (3.99); 2, 415 (5.86), 508 (4.87), 573 (4.33); 3, 413 (6.26),
526 (5.31); 4, 413 (6.10), 537 (4.86), 5, 418 (6.28), 548 (5.03); 6, 399 (6.20), 508 (5.17), 541
(4.67). 1H NMR data for 1 in CDCl3 (400 MHz): 8.81 (s, 8H, β-pyrrole-H), 8.33-8.35 (d, 8H, J =
1
8.00 Hz, o-phenyl-H), 8.04-8.06 (d, 8H, J = 8.00 Hz, m-phenyl-H), -2.84 (br, 2H, imino-H). H
NMR data for 3 in CDCl3 (500 MHz): 8.91 (s, 8H, β-pyrrole-H), 8.34-8.36 (d, 8H, J = 8.00 Hz,
1
o-phenyl-H) 8.04-8.06 (d, 8H, J = 8.00 Hz, m-phenyl-H). H NMR data for 5 in CDCl3 (500
MHz): 8.92 (s, 8H, β-pyrrole-H), 8.34-8.36 (d, 8H, J = 8.00 Hz, o-phenyl-H), 8.04-8.06 (d, 8H, J
= 8.00 Hz, m-phenyl-H). ESI-mass data of 1: 887.20 (calcd: 886.73).
X-ray crystal structure analysis
Suitable single crystals of the porphyrin ligand and its metal complexes were mounted on
a glass capillary and the data collections were performed on a Bruker AXS Kappa Apex II CCD
diffractometer with graphite monochromated Mo Kα radiation (λ = 0.71073 Å) at 298 K. The
reflections with I > 2σ(I) were employed for the structure solution and refinement. The SIR92
[17] (WINGX32) program was used for solving the structure by direct methods. Successive
Fourier synthesis was employed to complete the structures after full-matrix least squares
refinement on |F|2 using the SHELXL97 [18] software.
Hirshfeld surface analysis
Hirshfeld surface analysis and the generation of 2D fingerprint plots were performed
using Crystal Explorer 3.1 [14].
Antimicrobial studies
The antimicrobial activity of the free ligand and its metal complexes were performed
using the literature method [19] against MTCC cultures, which were obtained from the Microbial
4

culture collection, Chandigarh, India and are as follows: two gram-positive, Staphylococcus
aureus, Bacillus subtilis and two gram-negative Pseudomonas aeruginosa, Escherichia coli
bacterial strains, and the fungal strain Candida albicans. The ligand and its metal complexes
were dissolved in dimethylsulfoxide (DMSO) to a stock solution of 250 µg/mL. The sample was
loaded onto sterile discs on agar plates directly. Plates swabbed with the bacteria culture were
incubated at 35-37 °C for 24 hours. At the end of the incubation period, the inhibition zones
formed on the medium were evaluated in mm and studies were performed in duplicate. A solvent
control test was also performed in order to study the effect of dimethylsulfoxide on the growth of
the microorganism, but it showed no activity against the microbial strains. A standard
antimicrobial drug (tetracycline) was also screened under similar conditions for comparison.
Results and discussion
Synthesis of the porphyrin ligand and its metal complexes
The synthesis of 5,10,15,20-tetrakis-(4′-trifluoromethylphenyl)porphyrin H2T(4′-CF3P)P,
1, has been carried out using a modified procedure of Lindsey et al. [20] and its metal complexes
MT(4′-CF3P)P (M = Fe(II), 2; Ni(II), 3; Cu(II), 4; Zn(II), 5 and Pt(II), 6) were prepared by a
variant of the literature method [16,21,22]. The synthesized porphyrins were isolated, purified by
1
column chromatography and characterized by UV-Visible and H NMR spectroscopic methods,
mass spectrometry and single crystal X-ray diffraction analysis.
Photophysical properties of the porphyrins, 1-6.
The electronic absorption spectra of the porphyrin ligand and its metal complexes
exhibited an intense Soret (B) and four/two/one visible (Q) bands, and these absorption spectral
features are similar to those of the corresponding MTPPs [23]. The intensity of the Soret band is
high due to an allowed 1A1g → 1Eu transition and the peak position is in the range 413-418 nm in
dichloromethane as the solvent (except for 6, 399 nm). The overlayed UV-Visible spectra of 1-6
are shown in Fig. S1 and it is observed that there is a marginal red shifted absorption spectrum
for the zinc(II) complex and a marginal blue shifted absorption spectra for the iron(II), nickel(II)
and copper(II) complexes compared to that of the free ligand. As anticipated, the platinum(II)
complex undergoes a hypsochromic shift of 18 nm with respect to the free ligand, which is
attributed to the metal-to-ligand π-back bonding [24].
5

The fluorescent spectra of porphyrins 1-6 were studied in order to specify the effect of
the trifluoromethyl phenyl groups on the electronic properties of the porphyrins in the excited
state, using toluene as the solvent. Fig. S2 shows the fluorescence emission spectra of the various
fluorinated porphyrins under study. The fluorescent spectral pattern of the free ligand 1 is similar
to its tetraphenylporphyrin analogue (H2TPP), except for the fact that the peak intensity is low in
the former case, which is presumably due to the electron withdrawing nature of the
trifluoromethylphenyl groups (Fig. 2). On excitation at the Soret band, all the porphyrins exhibit
two well-defined emission bands in the range 598-718 nm, corresponding to the S1 → S0
transition, and another weak emission in the range 429-456 nm, corresponding to S2 → S0
transitions (Figure 2 and Table 1). Note, the S2 emissions of the free base porphyrins are too
weak to be detected, compared to the metalloporphyrins [25]. As reported earlier for ZnTPP, the
S2 emission is weak in intensity compared to the S1 emission for 5 [26]. Interestingly, we
observed the reverse case for the square planar nickel(II) and copper(II) complexes (3 and 4),
whereas for the iron(II) derivative, the S1 and S2 peak intensities are comparable.
418
1.0
Absorption
Emission
0.8
0.6
0.4
0.2
435
0.0
400
500
600
700
800
Wavelength (nm)
Fig. 2. Normalized emission (solid line) and absorption (dashed line) spectra of 1 in toluene at 298 K.
The Stokes shifts observed for porphyrins 1 and 5 are comparable to the corresponding
values for H2TPP and ZnTPP, which indicates that the structure of porphyrin in the excited state
is similar to that of the ground state (Table 1). Thus, by changing the phenyl ring to a
6

trifluoromethyl phenyl ring does not result in any structural reformation in the excited state. As
shown in Table 1, the S2 emissions exhibit a larger stokes shift compared to the S1 emissions of
the [Qx(0,0)] band [27]. The porphyrins 2-4 and 6 are weakly fluorescent compared to the free
ligand 1 and zinc(II) derivative 5, which may be due to the decay of the singlet excited state
through internal conversion in the former cases [28]. The S1 → S0 fluorescence quantum yields
(Φf) of the synthesized porphyrins 1-6 were measured in toluene using H2TPP as a reference [29]
(Φf = 0.11). It is obvious from Table 1 that the incorporation of trifluoromethyl groups at the
porphyrin periphery reduces the fluorescent quantum yield. Metalloporphyrins 2-4 and 6 show
very low quantum yields compared to the free ligand 1 which indicates that the metal
coordination may induce radiationless decay [30].
Table 1
Photophysical data of porphyrins 1-6 recorded in toluene at 300 K.
Porphyrin
Absorption
max (nm)
Fluorescencea
max (nm)
Quantum Yield Stokes Shift
(nm)
λ
λ
Φf
(S1-S0)
(S2-S0)
16 (5)b
H2TPP
418, 516, 552, 595, 647
424, 552, 588
418, 512, 552, 595, 645
415, 508, 573
426, 552
434, 455, 652, 716
430, 456, 598, 646
435, 454, 648, 713
440, 452, 601, 646
433, 454, 646, 711
434, 454, 651, 709
432, 450, 648, 708
429, 451, 650, 718
0.110
0.030
0.087
-
ZnTPP
2H, 1
06
17 (3)b
25
Fe(II), 2
Ni(II), 3
Cu(II), 4
Zn(II), 5
Pt(II), 6
-
07
417, 541
-
17
426, 552, 602
400, 508, 539
0.012
0.001
06
29
aFluorescence spectra of the porphyrins were obtained as a function of λex in the Soret band. bStokes shifts values
given in parenthesis correspond to the S1 emission of the [Qx(0,0)] band.
Structural description of porphyrins, 1, 3, 4 and 5.
We successfully characterized single crystals of the porphyrins, 1, 3, 4 and 5, which were
grown at room temperature by the vapor diffusion method using appropriate solvents, and the
data collections were also performed at room temperature (Table 2). Compounds 1 and 4
7

crystallized in the triclinic system, whereas 3 and 5 crystallized in the monoclinic system. In all
the compounds, the solvent molecule THF is either present in the crystalline lattice or bonded to
the metal centre. The bound or unbound THF solvate molecules in all the porphyrins show the
well known envelope conformation as observed in the literature [31,32]. The asymmetric unit of
1 consists of two half molecules of the porphyrin and two THF molecules, in which the
porphyrin planes are found to be planar in both molecules. The ORTEP and packing diagrams of
1 are shown in Figs. 3a and 3d respectively. It is reported in the literature that the free ligand and
copper(II) complex are isostructural in most porphyrins [32-34].
Table 2
Crystal structure data of the porphyrins under study: 1, H2T(4′-CF3P)P⋅(THF)2; 3, NiIIT(4′-CF3P)P⋅(THF)2; 4,
CuIIT(4′-CF3P)P⋅(THF); 5, ZnIIT(4′-CF3P)P⋅(THF).
1
C56H42F12N4O2
1030.94
1013690
purple
3
4
5
Empirical formula
fw
CCDC no.
Colour
C56H40F12N4 NiO2 C52H32CuF12 N4O C52H32F12 N4OZn
1087.63
1013689
violet
1020.36
1011088
brown
1022.19
1011087
brown
Crystal system
Space group
a, Å
b, Å
c, Å
α, (deg)
β, (deg)
triclinic
P-1
monoclinic
P21/n
14.5791(19)
9.5303(19)
18.351(4)
90.0
101.571(8)
90.0
2498.0(8)
2
triclinic
P-1
monoclinic
P21/c
19.427(3)
9.3940(10)
25.466(5)
90.0
102.756(5)
90.0
4532.8(12)
4
11.5014(8)
13.1179(12)
17.3269(15)
96.329(3)
92.833(3)
108.739(3)
2450.5(4)
2
9.7136(5)
14.5452(9)
16.8870(13)
76.608(3)
89.617(3)
76.676(3)
2255.8(3)
2
γ, (deg)
Volume (Å3)
Z
Dcalcd (Mg/m3)
λ, Å
1.397
0.71073
1.446
0.71073
1.502
0.71073
1.498
0.71073
T (K)
173
173
173
173
No. of unique
reflections
No. of parameters
refined
8528
4413
7810
7986
788
397
825
813
GOF on F2
1.027
0.0657
0.1849
1.015
0.0477
0.1179
1.039
0.0476
1.022
0.0465
0.1129
b
R1
c
wR2
0.1205
aR1 = Σ||Fo|–|Fc||/Σ|Fo|; Io > 2σ (Io). bwR2 = [Σ w(Fo –Fc2)2/Σw(Fo ) ] .
2
2 2 1/2
Interestingly, the porphyrin core in 1 exhibits a planar skeleton whereas in 4 it is non-
planar, possibly due to the presence of the 4-trifuloromethylphenyl groups and an extra THF
molecule in 1 compared to 4, which makes them non-isostructural. In compound 3, the
asymmetric unit contains half a molecule of the porphyrin and one THF molecule coordinated to
8

the nickel(II) centre. The ORTEP diagram of 3 consists of a nickel(II) ion which is hexa-
coordinated with two THF molecules in apex positions (Fig. 3b), and the molecular crystal
packing diagram is shown in Fig. 3e, formed through C−F···H(sol) interactions.
(a)
(d)
(b)
(e)
(c)
(f)
Fig. 3. ORTEP diagrams of (a) 1, H2T(4′-CF3P)P(THF)2 (solvent molecules and hydrogens are not shown for clarity,
thermal ellipsoids are shown at the 40 % probability level); (b) 3, NiT(4′-CF3P)P(THF)2 and (c) 5, ZnT(4′-
CF3P)P(THF). Slip-stack orientations of molecules of (d) 1, (e) 3 and (f) 5 through C−H···π; C−F···H(sol) and
C−F···H(sol) interactions respectively.
The first crystal structure of a six coordinated nickel(II) complex was reported by Schedit
et al., formed by the addition of a large excess of imidazole ligands to a diamagnetic square
planar nickel(II) porphyrin, which results in a high spin d8 complex [35]. Similarly, a few more
reports on high spin nickel(II) complexes of tetraphenylporphyrins bearing β-pyrrole electron
withdrawing substituents [36-38] are available in the literature, which were prepared either by
diffusing pyridine into the solution or treating the nickel(II) solution with a large excess of 1-
methylimidazole at room temperature.
9

It is observed that the presence of either bulkier or electron withdrawing groups at the β-
pyrrole positions makes the porphyrin core non-planar, which subsequently allows the effective
installation of a high spin nickel(II) ion at the porphyrin centre [35-39]. Also, there is a
lengthening of the Ni-N(pyr) bond distance in high spin nickel(II) porphyrins compared to that of
low spin complexes, which is presumably due to the presence of one unpaired electron in the dz2
2
orbital transferred from dx −y2. Along similar lines, the elongated Ni-N(pyr) bond length in the
planar high spin nickel(II) complex 3 is 2.051 Å, whereas the reported low spin non-planar
nickel(II) centre in the MTF4DMAP porphyrin [10] is 1.938(3) Å. This elongation of the bond
length in the high spin nickel(II) complex 3 is comparable with the reported high spin complexes
of planar Ni(II)-porphine (2.038(4) Å) [35] and non-planar Ni(II)-porphyrin (2.057(2) Å) [36].
0.4612 0.5494
0.1719
-0.0849
-0.2533
-0.4819
0.3093
0.1068
(a)
(b)
(c)
0.1288
N2
-0.1985
-0.5452
-0.0977
Cu1 0.0070
-0.1352
N1
N3
-0.4706
-0.2306
-0.0154
0.2380
-0.6017
-0.2662
-0.0251
0.2454
N4
0.1242
0.5227 0.5419
(d)
Fig. 4. ORTEP diagrams of 4, CuT(4′-CF3P)P (THF). (a) top view; (b) side view (the solvent molecule is not shown
for clarity; thermal ellipsoids are shown at the 40 % probability level); (c) mean plane displacements of the Cu(II)
ion and the core atoms shown in Å units; (d) slip-stack orientation of molecules through C−H···π interactions in 4,
CuT(4′-CF3P)P (THF) viewed down the ‘c’ axis.
In addition, the N-Ni-N(adj) and N-Ni-N(opp) bond angles in 3 were found to be 90.0(10)°
and 180.0(10)°, indicating the perfect planar geometry of the porphyrin core. The dihedral angles
between the porphyrin mean plane and 4-trifluoromethylphenyl groups are 83.44 and 63.89°.
Thus, due to the influence of the 4-trifluoromethylphenyl groups, the successful fitting of a hexa
10

coordinated nickel(II) ion was achieved without having β-pyrrole substituents at the porphyrin
periphery.
The copper(II) centre in 4 is four coordinated by the inner core nitrogen atoms of the
porphyrin ring, and there is an extra THF molecule present in the lattice. The porphyrin core in 4
exhibits non-planarity and the mean plane displacement of the core atoms is 0.3313 Å, which
is less compared to that of the reported β-pyrrole substituted copper(II) porphyrins [40,41]. The
dihedral angles between the mean plane of the porphyrin core atoms and the 4-
trifluoromethylphenyl groups are 89.72, 87.60(4), 56.39 and 87.50°. The ORTEP diagrams (top
and side view) and packing diagram showing the slip-stack orientation of the molecules through
C−H···π interactions are also shown in Fig. 4. The non-planarity of the core is possibly due to the
4-trifluoromethylphenyl groups and solvent (THF) molecule present in the lattice.
The zinc(II) centre in 5 is five coordinated and exhibits a domed shape which is quite
well known for zinc(II) complexes. The least square mean plane calculation indicates that the
porphyrin plane with the metal atom is almost planar and the mean plane deviation of the core
atoms is 0.0673 Å. However, the nitrogen atoms N3 and N4 are above the plane by 0.078(3)
and 0.045(3) Å, whilst the N1, N2 and Zn atoms are below the plane by 0.107(3), 0.074(3) and
0.218(1) Å respectively [42]. The bound THF molecule is responsible for the metal being
slightly pulled down from the mean plane. The 4-trifluoromethylphenyl groups make dihedral
angles of 82.91(1), 86.24(1), 86.27(1) and 68.95(1)° with the porphyrin mean plane. The average
Zn–N distance in 5 is 2.051(3) Å, relatively higher than the reported four coordinated ZnTPP
(2.037(2) Å) and quite similar to that of five coordinated Zn(II) complexes [9,43]. The average
Zn−O distance in 5 is found to be 2.23(14) Å, which is in good agreement with the values for the
reported penta-coordinated Zn(II) complexes [9,43].
Like our earlier report on fluorinated porphyrins, there is an absence of either direct π−π
interactions or intramolecular interactions in 1, 3, 4 and 5 [9,33]. The molecular crystal packing
consists of a number of intermolecular interactions involving carbon, fluorine, hydrogen, oxygen
and nitrogen atoms, viz. (sol/ph/pyr)C−H···F, (sol/ph/pyr)C−H···C(sol/ph/pyr), C−F···C(ph/pyr), (ph/pyr)H···H(sol),
(pyr)C−H···O(sol) and F···F (Table 3). Interestingly, the H···H close contact is seen only in 4 and 5,
and the distance varies from 1.845 to 2.364 Å, which is considerably shorter compared with the
previously reported fluorinated porphyrins, and this can be further supported by the Hirshfeld
surface analysis discussed later.
11

Table 3
Distances (in Å) for the different types of interactions in the crystal packing of porphyrins 1, 3, 4 and 5.
Interactionsa
(ph)C−H···C(pyr)
(sol)C−H···C(ph)
(ph)C−H···C(sol)
(pyr)C−H···C(sol)
(pyr)C−H···O(sol)
(ph)C−F···C(ph)
(ph)C−F···C(pyr)
(ph)C−F···H(sol)
(ph)C−F···H(ph)
(ph)C−F···H(pyr)
(pyr)H···H(sol)
1b
3b
4b
5b
2.727-2.895 (16)
-
-
-
-
-
-
-
2.723-2.884 (12)
2.763-2.872 (4)
2.888-2.890 (4)
-
-
-
-
-
-
2.658 (2)
2.787 (2)
2.844-2.898 (12)
2.566-2.573 (8)
3.152-3.167 (8)
-
-
-
-
-
3.132 (2)
2.582 (2)
2.590-2.595 (4)
2.641 (2)
2.335 (2)
-
-
2.574 (4)
2.642-2.670 (8)
-
-
-
-
2.618 (4)
2.669 (4)
-
2.664-2.670 (4)
2.322 (2)
1.845-2.364 (6)
-
-
-
-
(ph)H···H(sol)
F···F
2.853 (4)
-
a
b
Different types. The value in parenthesis gives the number of interactions of each type per molecule.
Hirshfeld surface analysis
In order to understand and visualize the intermolecular interactions quantitatively,
Hirshfeld surfaces (HSs) and 2D fingerprint plots (FPs) were generated using Crystal Explorer
3.1 [14]. The HSs, which have been mapped over a dnorm range of -0.14 to 2.0 Å, are illustrated in
Fig. 5. The red spots on the HSs indicate the presence of close contacts, whereas areas without
close contacts are shown as blue spots.
1
2
3
4
Fig. 5. Hirshfeld surfaces of porphyrins 1, 3, 4 and 5 with dnorm mapped ranging from -0.14 (blue) to 2.02 (red).
The crystal packing in porphyrins 1, 3, 4 and 5 is mainly controlled by the close contacts
involving fluorine, i.e. F···H, which are observed as intense red spots on the HSs. The F···F
contacts are also seen as large intense red spots in porphyrins 1, 3 and 5. The F···C contacts are
observed as medium intense red spots in the free ligand 1 and its copper derivative 4, compared
12

to a faint red area in the zinc derivative 5. Apart from this, porphyrin 5 shows faint red spots for
N···F close contacts. In addition to the close contacts involving fluorine, C···H contacts appear as
intense and/or faint red spots in porphyrins 1 and 4. Interestingly, unlike our recent report on the
fluorinated porphyrins MT(2′,6′-DFP)P [33] and MTF4DMAP [9], H···H contacts are observed
as red spots in 1 and 3, being very intense in the latter case. The shapes of the FPs of the
porphyrins in 1, 3, 4 and 5 are incomparable, indicating that there are no isostructural pairs,
which is further supported by the geometrical data discussed earlier (Table 3). The FPs of 1, 3, 4
and 5 feature spikes of various length and thickness, the most dominant of which is the F···H
contacts in the middle region of each plot (Fig. 6). In 3 and 4, 44 % of the intermolecular
contacts are associated with F···H contacts, whereas in 1 and 5 they are associated with 36 % and
39 % of the HSs respectively.
F…C 5.5 %
1
1
1
1
1
C…H 17.5 %
F…H 36 %
F…H 43.4 %
F…H 43.6 %
F…H 39.3 %
F…F 3.5 %
F…F 5.4 %
F…F 5.4 %
F…F 7.4 %
H…H 30 %
H…H32.1 %
H…H 22 %
1
2
C…H 12 %
2
2
F…C 4.7 %
2
2
2
F…C 3.8 %
3
3
3
3
3
C…H14 %
3
F…C 6.5 %
4
4
4
4
4
C…H 13.5 %
H…H 28 %
4
Fig. 6. Comparison of the full/decomposed FPs for the various intermolecular interactions of porphyrins 1, 3, 4 and
5.
The distance (di + de) is about 2.31 to 2.44 Å for porphyrins 1, 3, 4 and 5, which are
significantly shorter than the corresponding sum of the van der Walls radii (2.45-2.70 Å),
indicating the significant role in crystal packing [37-39]. The interactions involving fluorine
13

other than F···H contacts are F···F [4-5 % in 1, 3, 4; 7 % in 4] and F···C [4-7 % in 1, 3, 4 and 5]
with di + de values in the range 2.59-2.96 and 3.14-3.20 Å respectively, which are considerably
shorter than the reported values [9,33]. Also, the wing-like peripheral spikes for the C···H
contacts appear at the top left and bottom right of each plot, and the percentage contributions are
18, 12, 14 and 14 % respectively for 1, 3, 4 and 5. The FPs of the H···H contact are somewhat
closer in nature compared to the previously reported fluorinated porphyrins, and are especially
more prominent in 4, characterized by two sharp peaks, whereas for 1, 3 and 5 they are broader
in nature. [30 % in 1; 32 % in 3; 22 % in 4 and 28 % in 5]. Overall, the interactions involving
fluorine are 46 % for 1 and 53-55 % for 3−5, and these play a major role in directing the
supramolecular architecture of the porphyrins (Fig. 7). Apart from the interactions mentioned
above, the presence of other contacts, such as O···H, N···H and N···F interactions, are also
observed in 1, 3, 4 and 5.
5
4
3
1
13.5
14
39.3
6.5
7.4
28
5.3
C···H
F···H
F···C
F···F
43.6
3.8 5.4
22
11.2
12
43.4
4.7 5.4
32.1
2.4
H···H
Others
17.5
36
5.5 3.5
60
30
7.5
0
20
40
80
100
Fig. 7. Percentage contribution of non-covalent interactions in porphyrins 1, 3, 4 and 5 on the basis of HSs.
Antimicrobial studies of the porphyrin ligand and its metal complexes
The free ligand and its metal derivatives, 1-6, were tested for their in vitro antimicrobial
activity against four bacterial strains and one fungal strain by the well diffusion method at
different concentrations (50, 75 and 100 µg/mL). The commercially available standard drug
tetracycline was used as a control and the zones of inhibition against the control are shown in
Fig. 8. All the porphyrins manifested different impacts on the different organisms. The
antimicrobial activity of H2TPP was examined under similar conditions and the results reveal
that the non-fluorinated analogue shows a lesser activity compared to the fluorinated analogue
14

(Fig. 8). It was observed that porphyrins 1-6 showed the maximum zone of inhibition at the
maximum concentration. At a concentration of 100 µg/mL, porphyrin 3 showed a maximum
zone of inhibition of 19 mm against E.coli, 1 showed inhibition zones of 18 mm against E. coli
and B. subtilis, 4 and 5 showed 15 and 17 mm of inhibition zones respectively against E.coli. At
75 µg/mL concentration, a maximum zone of inhibition of 16 mm was recorded for 3, followed
by 15 and 14 mm for 6 and 4 respectively against E. coli. At 50 µg/mL of concentration, a
maximum zone of inhibition was recorded on 3 against E. coli, followed by 6 and 1 against B.
subtilis. There was no activity observed for compounds 4 and 6 against B. subtilis or for 2 and 3
against P.aeruginosa. In the case of the fungal strain C. albicans, the maximum activity was
found for porphyrin 2, followed by 3 and no activity was found for 5 (Fig. 8). Among all the
compounds, the antimicrobial activity of the free base porphyrin showed the maximum zone of
inhibition towards all five microorganisms and the order of activity is as follows: 1 > 3 > 2 > 4 >
5 > 6. Overall, the structure of the cell membrane may be altered by the porphyrin molecules due
to their affinity to biological organisms and this could be the reason for the biological activity
[44].
20
15
10
5
0
H2TPP
S.aureus
2H, 1
Fe(II), 2
B.subtilis
Ni(II), 3
E.coli
Cu(II), 4
Zn(II), 5
Pt(II), 6
P.aeruginosa
C.albicans
Fig. 8. Comparison of the antimicrobial activities of the studied porphyrins 1-6 along with H2TPP.
15

Conclusions
In conclusion, the synthesis and photophysical properties of a fluorinated porphyrin
and its metal derivatives were explored. Steady state fluorescence spectra of the
porphyrins
states. The fluorescent quantum yield is higher for the free ligand and the zinc(II)
derivative compared to the other metal derivatives. Compounds and have been
1-6 exhibit dual emission bands originating from the S2 → S0 and S1 → S0
1
3-5
structurally characterised using experimental crystallographic studies along with
computational analysis. The geometrical and Hirshfeld surface analyses indicate that the
free ligand
1 and copper(II) complex 4 are non-isostructural, which may be possibly due
to the influence of the trifluoromethylphenyl groups and the difference in the solvated
THF molecule(s). The effective installation of a six coordinated nickel(II) ion with two
THF molecules present at the apex positions in the planar porphyrin core was successfully
achieved. Compounds
molecules to orient in a slip-stack fashion, leading to 2D networks, whereas in
contain C···H interactions. From the FPs, it can be concluded that the back bone of the net
supramolecular arrangements are dictated by close contacts involving fluorine [46 % for
and 53-55 % for ]. The antibacterial and antifungal activities of all the synthesised
3
and
5
showed several F···H interactions which allow the
1
and
4
1
3-5
porphyrins were examined and the results show that the free ligand is highly effective
compared to its metal derivatives; also their inhibitory capabilities are concentration
dependent.
Acknowledgements
The authors, SS (SR/WOS-A/CS-146/2011) and CA (SR/FT/CS-25/2011, SB/EMEQ-
016/2013) thank DST, New Delhi for financial support. We also thank Dr. Shibu M Eappen,
STIC, CUSAT, Kochi and Dr. Babu Varghese, SAIF, IIT Madras for the single crystal data
collection and structure solution, refinement respectively.
Appendix A. Supplementary Data
CCDC 1013690, 1013689, 1011088 and 1011087 contain the supplementary crystallographic
data for porphyrins 1, 3, 4 and 5. These data can be obtained free of charge via
http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data
16

Centre, 12 Union Road, Cambridge, CB2 1EZ, UK; Fax: + 44 123 336 033; or e-mail:
deposit@ccdc.cam.ac.uk.
References
[1] K.M. Kadish, K.M. Smith, R. Guilard, (Ed.), The Porphyrin Handbook, Academic Press,
San Diego, CA, 2000, vol. 1-20.
[2] (a) J.-H. Chou, M.E. Kosal, H.S. Nalwa, N.A. Rakow, K.S. Suslick in The Porphyrin
Handbook, Academic Press, San Diego, CA, 2000, vol. 6, 43-131;
(b) Y. Feng, J. Cheng, L. Zhou, X. Zhou, H. Xiang, Analyst, 137 (2012) 4885-4901.
[3] T. Goslinski, J. Piskorz, J. Photochem. Photobiol. C: Photochem. Rev. 12 (2011) 304-321.
[4] S. Rani-Beeram, K. Meyer, A. McCrate, Y. Hong, M. Nielsen, S. Swavey, Inorg. Chem.
47 (2008) 11278-11283 and references therein.
[5] I. Ojima (Ed.), Fluorine in Medicinal Chemistry and Chemical Biology; Wiley-Blackwell:
UK, 2009.
[6] K.L. Kirk, J. Fluor. Chem. 127 (2006) 1013-1029.
[7] (a) J.A. Olsen, D.W. Banner, P. Seiler, B. Wagner, T. Tschopp, U. Obst-Sander, M.
Kansy, K. Muller, F. Diederich, ChemBioChem. 5 (2004) 666-675;
(b) B.E. Smart, J. Fluor. Chem. 109 (2001) 3-11.
[8] K.M. Barkigia, P. Battioni, V. Riou, D. Mansuy, J. Fajer, Chem. Commun. (2002)
956−957.
[9] R. Soman, S. Sujatha, S. De, V.C. Rojisha, P. Parameswaran, B. Varghese, C.
Arunkumar, Eur. J. Inorg. Chem. (2014) 2653-2662.
[10]I. Goldberg, CrystEngComm. 4 (2002) 109-116.
[11]S.G. DiMagno, J.C. Biffinger, H. Sun, Fluorinated Porphyrins and Corroles:
Synthesis, Electrochemistry, and Applications, Fluorine in Heterocyclic Chemistry,
Vol. 1, 2014, pp 589-620.
[12]P.A. Stuzhin, Fluorinated Phthalocyanines and Their Analogues, Fluorine in
Heterocyclic Chemistry, Volume 1, 2014, pp 621-681.
17

[13]S.K. Pandey, A.L. Gryshuk, A. Graham, K. Ohkubo, S. Fukuzumi, M.P. Dobhal, G.
Zheng, Z. Ou, R. Zhan, K.M. Kadish, A. Oseroff, S. Ramaprasad, R. K. Pandey,
Tetrahedron 59 (2003) 10059-10073.
[14]S.K. Wolff, D.J. Grimwood, J.J. McKinnon, M.J. Turner, D. Jayatilaka, M.A. Spackman,
Crystal Explorer 3.1 (2013), University of Western Australia, Crawley, Western Australia,
2005-2013; http://hirshfeldsurface.net/CrystalExplorer.
[15]D.D. Perrin, W.L.F. Armarego, Purification of Organic Solvents, Pergamon Press,
Oxford, 1988.
[16]R.C. Kwong, S. Sibley, T. Dubovoy, M. Baldo, S.R. Forrest, M.E. Thompson, Chem.
Mater. 11 (1999) 3709-3713.
[17]A.G. Altomare, G. Cascarano, C. Giacovazzo, A. Gualardi, J. Appl. Crystallogr. 26
(1993) 343-350.
[18]G.M. Sheldrick, SHELXL97; University of Göttingen: Göttingen, Germany, 1997.
[19]D. Greenwood, R. Snack, J. Peurtherer, Medical Microbiology, A Guide to Microbial
Infections, Pathogenesis, Immunity, Laboratory Diagnosis and Control, 15th Ed, 1997.
[20]J.S. Lindsey, I.C. Schreiman, H.C. Hsu, P.C. Kearney, A.M. Marguerettaz, J. Org.
Chem. 52 (1987), 827-836.
[21]P. Bhyrappa, V. Krishnan, Inorg. Chem. 30 (1991) 239-245.
[22](a) P. Bhyrappa, S.R. Wilson, K.S. Suslick, J. Am. Chem. Soc. 119 (1997) 8492-8502;
(b) W. Wu, W. Wu, S. Ji, H. Guo, X. Wang, J. Zhao, Dyes Pigm. 89 (2011) 199-211;
(c) X. Wang, X. Chen, Z. Xie, X. Wang, Angew. Chem. 47 (2008) 7450-7453.
[23]M. Meot-Ner, A.D. Adler, J. Am. Chem. Soc. 97 (1975) 5107-5111.
[24]L.M. Mink, M.L. Neitzel, L.M. Bellomy, R.E. Falvo, R.K. Boggess, B.T. Trainum, P.
Yeaman, Polyhedron, 16 (1997) 2809-2817.
[25]M. Gouterman, P.M. Rentzepis, Porphyrins: Excited States and Dynamics (ACS
Symposium Series) 1987.
[26]S. Tobita, Y. Kaizu, Y. Kobayashi, I. Tanaka, J. Chem. Phys. 81 (1984) 2962-2969.
[27](a) N. Venkatramaiah, B. Ramakrishna, A. R. Kumar, N. Veeraiah, R. Venkatesan, J.
Alloys Compd. 513 (2012) 318-323.
(b) K.P. Chandra Shekar, B. Mishra, A. Kumar, S. Phukan, S. Mitra, D. Kumar, J.
Porphyrins Phthalocyanines 14 (2010) 1034-1039.
18

[28]I. Gupta, M. Ravikanth, J. Chem. Sci. 117 (2005) 161-166.
[29](a) O. Ohno, Y. Kaizu, H. Kobayashi, J. Chem. Phys. 82 (1985) 1779-1787;
(b) P.G. Seybold, M. Gouterman, J. Mol. Spectrosc. 31 (1969) 1-13.
(c) M.M. Kruk, A.S. Starukhin, W. Maes, Macroheterocyles 4 (2011) 69-79.
(d) J. Karolczak, D. Kowalska, A. Lukaszewicz, A. Maciejewski, R.P. Steer J. Phys.
Chem. A 108 (2004) 4570-4575.
[30]T. Zoltan, F. Vargas, V. Lopez, V. Chavez, C. Rivas, A.H. Ramirez, Spectrochim. Acta
Part A Mol. Biomol. Spectrosc. 135 (2015) 747-756.
[31]C.A. Reed, T. Mashiko, W.R. Scheidt, K. Spartalian, G. Lang, J. Am. Chem. Soc.
102 (1980) 2302-2306.
[32]C.K. Schauer, O.P. Anderson, S.S. Eaton, G.R. Eaton, Inorg. Chem. 24 (1985) 4082-
4086.
[33]R. Soman, S. Sujatha, C. Arunkumar, J. Fluor. Chem. 163 (2014) 16-22.
[34]E.R. Birnbaum, J.A. Hodge, M.W. Grinstaff, W.P. Schaefer, L. Henling, J.A. Labinger,
J.E. Bercaw, H.B. Gray, Inorg. Chem. 34 (1995) 3625-3632.
[35]J.F. Kirner, J. Garofalo Jr, W.R. Scheidt, Inorg. Nucl. Chem. Lett. 11 (1975) 107-
112.
[36]H. Duval, V. Bulach, J. Fischer, R. Weiss, Inorg. Chem. 38 (1999) 5495-5501.
[37]P. Bhyrappa, M. Sankar, B. Varghese, Inorg. Chem. 45 (2006) 4136-4149.
[38]M.W. Renner, K.M. Barkigia, D. Melamed, K.M. Smith, J. Fajer, Inorg. Chem. 35 (1996)
5120-5121.
[39]A.L. Balch, M.M. Olmstead, S.L. Phillips, Inorg. Chem. 32 (1993) 3931-3936.
[40]P. Bhyrappa, C. Arunkumar, J. Chem. Sci. 122 (2010) 233-238.
[41]P. Bhyrappa, C. Arunkumar, B. Varghese, D.S. Sankara Rao, S.K. Prasad, J. Porphyrins
Phthalocyanines 12 (2008) 54-64.
[42]W.R. Scheidt, in The Porphyrin Handbook, Academic Press, New York, 2000, vol. 3, 49-
112.
[43]P. Bhyrappa, C. Arunkumar, J.J. Vittal, J. Chem. Sci. 117 (2005) 139-143.
[44]A. Hou, Z. Xue, Y. Liu, S. Qu, W. Wang, Chem. Biodivers. 4 (2007) 1492-1500.
19

20

Graphical abstract
Effect of trifluoromethylphenyl groups:
The free ligand and the copper(II) complex of MT(4′-CF3P)Ps are non-isostructural, being
influenced by intermolecular interactions involving trifluoromethylphenyl groups and solvent (THF)
molecules. It is evident from Hirshfeld surface analysis that the arrangements of the supramolecular
networks are dictated by the close contacts involving fluorine (F∙∙∙H) and other C∙∙∙H and H∙∙∙H contacts.
21