RSC Advances

View Article Online

PAPER View Journal | View Issue

Ternary Eu(III) and Tb(III) b-diketonate complexes

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

containing chalcones: photophysical studies and

Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

Cite this: RSC Adv., 2017, 7, 44272

biological outlook†
Zafar Abbas, Srikanth Dasari and Ashis K. Patra *

Four ternary lanthanide(III) complexes, namely [Eu(Anpp)(TTA)3] (1), [Tb(Anpp)(TTA)3] (2), [Eu(Pypp)(TTA)3] (3)
and [Tb(Pypp)(TTA)3] (4), [TTA ¼ 1,1,1-trifluoro-3-(2-theonyl)acetone, Anpp ¼ 3-(anthracen-9-yl)-1-
(pyridine-2-yl)prop-2-en-1-one, Pypp ¼ 3-(pyren-1-yl)-1-(pyridine-2-yl)prop-2-en-1-one] were
designed, synthesized and characterized by various spectroscopic techniques like FT-IR, 1H-NMR,
ESI-MS, UV-Vis and spectral emission studies. [Eu(Pypp)(TTA)3] (3) was structurally characterized,
showing an eight coordinated {EuN1O7} square antiprismatic geometry with one N,O-donor chalcone
and three O,O-donor b-diketonate ligands. Detailed photophysical properties like excited state lifetime
(s) and hydration number (q) were determined. The presence of three TTA ligands inhibits non-radiative
deactivation with lifetimes in H2O in the range of 0.306–0.445 ms. The calculated hydration number (q)
values (0.37–0.63) from the excited state lifetime measurements show the absence of any bound H2O
molecules in the coordinatively saturated complexes (q < 1). Complexes 1–4 were studied for their
biological interactions with DNA and protein and their DNA photocleavage activity was investigated. The
binding constants with CT-DNA (Kb ¼ 1.15–8.8  105 M1) and HSA (KHSA ¼ 6.5–8.1  105 M1) of
complexes 1–4 show their significant affinity towards these biological targets. Incorporation of chalcone
Received 2nd August 2017
Accepted 6th September 2017
ligands containing anthracene or pyrene as a photosensitizing moiety in these complexes were effective
in generating reactive oxygen species (ROS). Complexes 1–4 display moderate photocleavage of
DOI: 10.1039/c7ra08543e
supercoiled (SC)-DNA to its nicked circular (NC) form on exposure to UV-A light of 365 nm through the
rsc.li/rsc-advances generation of singlet oxygen (1O2) and hydroxyl radicals (cOH) under physiological conditions.

forbidden and have very weak absorption (3  0.1–1 M1 cm1),

Introduction therefore resulting in very faint luminescence, which can be
Lanthanide complexes have been widely explored as sensors, enhanced by attachment of a suitably chosen organic chromo-
MRI contrast agents, responsive optical probes, luminescent phore to excite the lanthanide by the so called ‘antenna effect’,
MOFs, display materials, chemo and radio therapeutic agents, which provides a large Stokes shi and avoids photo-
and cellular imaging agents owing to their intricate optical bleaching.4,5 Such indirect sensitization in fact relaxes the strict
properties and high redox stability of the trivalent Ln3+ state.1–11 selection rules that otherwise limit the f / f transitions in Ln3+
Lanthanides are used abundantly in various industries like and results in signicant luminescence enhancement.
optical, lighting, display, laser, ceramics, energy or non-invasive Currently polyaminocarboxylate gadolinium complexes, namely
imaging technologies. The very fascinating optical features of gadopentatic acid (Magnevist®) and gadoteric acid (Artirem®)
the lanthanide ions originate from their [Xe] 4fn (n ¼ 0–14) are in clinical use as magnetic resonance imaging (MRI)
electronic conguration because of shielded f-orbitals by the contrast agents, showing promising role of the lanthanides in
lled 5s and 5p orbitals, giving rise to various electronic levels of biomedical imaging.12 Photodynamic therapy is now being
dened energy which are hardly sensitive to the surrounding widely appreciated as a promising noninvasive methodology for
chemical environment. The f–f transitions are symmetry curb and cure of cancer which relies on the generation of
cytotoxic reactive oxygen species (mainly 1O2) by irradiating
some nontoxic photosensitizers at a specic wavelength, that
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, causes cell death in the region of irradiation.13–15 Photofrin®,
Uttar Pradesh, India. E-mail: akpatra@iitk.ac.in the rst clinically accepted PDT agent, is an oligomeric mixture
† Electronic supplementary information (ESI) available: ESI-MS gures; unit cell of natural hematoporphyrin, generates reactive oxygen species
packing diagram; selected bond distances and angles; photophysical aspects;
(1O2) in a type II energy transfer pathway at 633 nm.14–16 Weak
lifetime measurements; DNA and protein binding plots; DNA cleavage data.
CCDC 1566126. For ESI and crystallographic data in CIF or other electronic
absorbance in phototherapeutic window, prolonged skin
format see DOI: 10.1039/c7ra08543e sensitivity and hepatotoxicity are the major drawbacks with

44272 | RSC Adv., 2017, 7, 44272–44281 This journal is © The Royal Society of Chemistry 2017
 View Article Online

Paper RSC Advances

porphyrin-based PDT agents.17,18 Although there are several effect of highly electron withdrawing –CF3 group decreases the
transition metal complexes in the literature showing remark- non-radiative loss of Ln(III) excited state energy compared to the
able photocytotoxicity and DNA photocleavage activity, very few high energy C–H oscillators, resulting in enhanced lumines-
are reported with lanthanides.19–24 Lanthanide(III) complexes cence intensity and rigidity of the complexes due to tight bond
with a range of coordination numbers ranging from 7–12 and between ligand and Ln(III).26,27 The choice of two different
unusual optical properties will be niche in the development of chalcones as secondary ligands having a,b-unsaturated ketone
efficient photocytotoxic agents and the excellent redox stability as central core conjugated to anthracene or pyrene as light
of Ln(III) is also benecial for their use in biological media harvesting photosensitizing moiety. Chalcones show various
against various reducing agents in biology like thiols and biological effects like anti-inammatory, anticancer, antima-
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

ascorbates. Some of the Ln(III) ions have the advantage of bright larial, antifungal, anti-infective activity and some other features
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

visible light luminescence over other lanthanides and transition like sensing to non-linear optics.28–33 Moreover these moieties
metals and they have been widely explored as sensors in phys- can also act as DNA intercalators and photosensitizers. We have
iological conditions or in bioassays.4–7 Currently we are evaluated biological interaction of complexes 1–4 with nucleic
exploring luminescent Ln(III) complexes for their interaction acid and protein. They show good binding affinity towards ds-
with biological targets, photoinduced DNA cleavage activity and DNA through the intercalation of planar aromatic pyrene and
cellular imaging agents.24 anthracene moieties between the DNA base pairs. HSA binding
We describe here, four lanthanide complexes of Eu(III) and affinity was determined by quenching in emission of Trp-214
Tb(III) viz. [Eu(Anpp)(TTA)3] (1), [Tb(Anpp)(TTA)3] (2), residue. They exhibit photoinduced DNA photocleavage
[Eu(Pypp)(TTA)3] (3) and [Tb(Pypp)(TTA)3] (4) [TTA ¼ 1,1,1- activity through the generation of singlet oxygen (1O2) in Type-II
triuoro-3-(2-theonyl)acetone, Anpp ¼ 3-(anthracen-9-yl)-1- pathways and cOH involving photoredox pathway at physiolog-
(pyridine-2-yl)prop-2-en-1-one, Pypp ¼ 3-(pyren-1-yl)-1- ical conditions.
(pyridine-2-yl)prop-2-en-1-one], were synthesized, character-
ized and studied for their photophysical properties and inter- Results and discussion
action with DNA and serum proteins along with photoinduced
DNA cleavage activity. The complexes containing three anionic Synthesis and general aspects
b-diketonate ligand and one bidentate chalcone conjugated to Herein, we have synthesized two chalcone derivatives namely
a urophore have been designed as coordinatively saturated Anpp [(E)-3-(anthracen-9-yl)-1-(pyridin-2-yl)prop-2-en-1-one]
systems to avoid non-radiative transitions from the Ln(III) and Pypp [(E)-3-(pyren-1-yl)-1-(pyridin-2-yl)prop-2-en-1-one] by
excited states through vibrational energy transfer (VET) to O–H, Claisen–Schmidt condensation reaction and characterized by
N–H and C–H oscillators (Scheme 1).2,4,7,25 The b-diketonate 1
H-NMR, UV-Vis and ESI-MS studies.34,35 Four TTA-based
ligands having various conjugated aromatic planar groups are lanthanide complexes containing these chalcones were then
established as efficient sensitizers in developing visible light synthesized by reacting a solution of Ln(TTA)3$2H2O in THF
emitting lanthanide (Eu3+, Sm3+ and Tb3+) complexes. Use of with chalcones (Scheme 2). Complexes were isolated in good
polyuorinated b-diketonates have the advantage over non- yields and characterized by FT-IR, ESI-MS, UV-Vis and emission
uorinated ones because of the vibrational energy of the C–H spectroscopy and through structural determination of complex
oscillator (n ¼ 2800–3000 cm1) is higher than that of C–F 3 by single crystal X-ray crystallography. FT-IR spectra shows
oscillator (n ¼ 1120–1350 cm1). Fluorination induced inductive a lowering in frequency in the stretching vibrations of C]O and
C]C bonds from 1676 and 1632 cm1 in the free HTTA to
around 1600 and 1535 cm1 in the complexes 1–4 while the
bands at 490 cm1 correspond to nLn–O stretching vibrations
and at 519 cm1 to Ln–N stretching vibrations.26b,26c,36,37 ESI-MS
spectra of the complexes 1, 2 and 4 assignable to [M-TTA]+ and
for complex 3 to [M  Na]+ in DMF with matching isotopic
distribution proles indicating the formation of complexes 1–4
(Fig. S1, ESI†).
The UV-Vis absorption spectra of the complexes show the
ligand-centered absorption band corresponding to p–p* tran-
sitions in the range of 270 to 480 nm. Complexes 1 and 2 con-
taining Anpp ligand displayed close resemblance in their
absorption spectra with lmax at 270 nm and 346 nm originated
from the Anpp and TTA ligands. On the contrary, complexes 3
and 4 with Pypp ligands shows overlapping spectra with lmax at
Scheme 1 Schematic design principle for complexes 1–4 showing 273 nm, 346 nm and 440 nm originated from the Pypp and TTA
deactivation of Ln* in [Ln(TTA)3(H2O)2] via nonradiative vibrational
ligands (Fig. 1(a), S2 and S3 in ESI†). Close resemblance in the
energy transfer (VET) through lanthanide coordinated H2O (left); incor-
poration of bidentate chalcones inhibit this quenching with increased UV-Vis spectra of 1–4 with identical ligands is independent of
emission intensity (middle) and representation of [Ln(chalcone)(TTA)3] Ln(III), also suggests minimal or no perturbation of the elec-
(1–4) with luminescence from of Eu3+ and Tb3+ (right). tronic levels of Ln(III). Absorption spectra of the complexes 1–4

This journal is © The Royal Society of Chemistry 2017 RSC Adv., 2017, 7, 44272–44281 | 44273
 View Article Online

RSC Advances Paper

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

Scheme 2 Synthetic route for the chalcone ligands and [Ln(chalcone)(TTA)3] (1–4) complexes.

The lower s value for complex 4 possibly due to the smaller

energy gap between the 5D4 state of Tb3+ and the triplet excited
state of TTA moiety, that may result in thermal back energy
transfer processes and consequently an ineffective radiative
transition from Tb3+ 5D4 excited state.38 Solution state specia-
tion of complexes in aqueous media was established by
recording their excited state lifetimes in H2O and D2O. Their
hydration number (q) was calculated using modied Horrock's
equation that gave values less than one, conrming the absence
Fig. 1 (a) UV-visible absorption spectral traces of complexes 1–4 ([1] of H2O molecule in the complexes summarised in Table 1
and [2] ¼ 20 mM, [3] and [4] ¼ 15 mM) in DMF at 298 K. (b) Time-delayed
(Fig. S6, ESI†).39 Absence of H2O molecule at Ln(III) center arrest
luminescence spectra for complexes 1 and 2 at 298 K. [delay time ¼
0.1 ms, gate time ¼ 0.1 ms, lex ¼ 340 nm, slit width ¼ 10 nm, [1] and the nonradiative vibrational energy transfer (VET) from Ln(III) to
[2] ¼ 20 mM]. O–H oscillators of Ln(III) bound H2O, thus results in longer
lifetimes.

in DMF recorded for a period of 4 h at 298 K shows no appre- Crystal structure determination
ciable change in the band intensity suggesting their stability in
solution state (Fig. S4, ESI†). [Eu(Pypp)(TTA)3] (3) have been structurally characterized by
single crystal X-ray diffraction studies. It was crystallized in
triclinic crystal system with space group P1 as mononuclear
Photophysical properties discrete molecule having two molecules in the unit cell. The
Time-delayed luminescence spectra of the complexes shows ORTEP view of complex 3 along with coordination polyhedron
emission bands corresponds to 5D0 / 7FJ (J ¼ 0–4) and 5D4 / of lanthanide core have been shown in Fig. 2. It has an eight
7
FJ (J ¼ 6–3) transitions for Eu3+ and Tb3+ respectively (Fig. 1(b)). coordinated {EuN1O7} coordination geometry around the
Excited state lifetime of the complexes in H2O were found in the europium centre, two of which originates from a bidentate
range of 0.306 ms to 0.445 ms are depicted in Table 1 (Fig. S5,
ESI†).

Table 1 Selected physiochemical and photophysical data for

complexes 1–4

Complexes IRa (cm1) nC]O sDMFb (ms) sH2Oc (ms) sD2Od (ms) qe

Complex 1 1601 (s) 464 445 633 0.50

Complex 2 1603 (s) 420 395 426 0.62
Complex 3 1602 (s) 457 390 560 0.63
Complex 4 1602 (s) 391 306 319 0.37
a
IR vibrational stretching frequency in KBr phase. b Excited state
lifetime (s  15%) measured in DMF. c Excited state lifetime (s 
15%) measured in H2O. d Excited state lifetime (s  15%) measured Fig. 2 (a) ORTEP view of [Eu(Pypp)(TTA)3] (3) with thermal ellipsoids
in D2O. e Hydration number (q  10%) determined using modied drawn at the 50% probability level. (b) The {EuN1O7} coordination
Horrock's equation. polyhedra of the Eu(III) core showing distorted square antiprism
geometry.

44274 | RSC Adv., 2017, 7, 44272–44281 This journal is © The Royal Society of Chemistry 2017
 View Article Online

Paper RSC Advances

N,O-donor neutral chalcone ligand and the other six from three Electronic absorption spectral studies. DNA binding inter-
monoanionic bidentate O,O donor TTA ligands, that can be best action studies of the complexes were carried out through UV-Vis
described as distorted square antiprismatic geometry. Here absorption spectral titration. Absorption spectra was recorded
each square-plane is constituted from N1, O1, O6, O7 and O2, with increasing concentration of CT-DNA at a constant complex
O3, O4, O5 atoms respectively with a dihedral angle of 4.75 concentration in order to determine the intrinsic binding
between them (Fig. 2(b)). At the center of the square antiprism constant Kb in 5 mM Tris HCl–NaCl buffer (pH ¼ 7.2) (Fig. 3(a)
lies Eu(III) with a distance of 1.251 Å to the oxygen containing and S8–S10 in ESI†). Signicant hypochromism of ligand-
plane and 1.440 Å to the opposite plane for complex 3. Eu–N(1) centered bands was observed with the addition of CT-DNA,
and Eu–O(1) bond lengths of the neutral chalcone were 2.608(6) indicative of an intercalative binding mode of the complexes
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

and 2.453(5) Å respectively. On contrary, Eu–O bond distances through stacking of planar aromatic chromophore (Anpp and
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

from the anionic TTA was found in the range from 2.349(5) to Pypp) between the base pairs of DNA. The Kb values of the order
2.375(6) Å. The :N–Eu–O bite angle for the chalcone ligand was of 105 M1, suggests a strong binding affinity of the complexes
62.43(18) while :O–Eu–O bite angle for TTA ligands were 1–4 with DNA (Table 2).
ranging from 71.02(19)–72.15(19) . All the selected major bond Ethidium bromide displacement studies. Ethidium bromide
lengths and bond angles have been listed in the Table S1, ESI.† (EB), a planar cationic dye, which is capable of binding with ds-
Unit cell packing diagram have been given in Fig. S7 in ESI.† DNA via intercalation between the base pairs. A competitive
binding assay of the complexes 1–4 with CT-DNA was performed
by recording the changes in emission intensity of EB-DNA
adduct by incremental addition of complexes. Fluorescence
DNA binding studies
emission of EB in buffer is quite weak because of the quenching
For the development of potential chemotherapeutic agents, from the solvation. Addition of DNA results in 25 fold increase
DNA has been the primary biological target of many pharma- in emission intensity due to stacking of phenanthridine moiety
cologically active drugs. These drug molecules mainly bind with between the base pairs.42,43 Apparent DNA binding constant
the target either through covalent or noncovalent interactions. (Kapp) was calculated from eqn (2) by calculating concentration
There have been two major classes of noncovalent DNA binding required for 50% quenching (C50) in emission of the EB-DNA
agents: intercalators and groove binders. Intercalation involves adduct (Fig. 3(b) and S11–S13 in ESI†). The values of Kapp
the insertion of planar moiety between the DNA base pairs, shown in Table 2 was in the range of 107 M1, displayed
resulting a decrease in DNA helical twist and its elongation a signicantly strong binding of the complexes with DNA by
whereas groove binding does not affect large conformational displacing EB from DNA.
changes which t into the major or minor grooves of DNA.40,41
Human serum albumin (HSA) binding studies
Serum albumin is the most abundant protein in human blood
plasma (around 40 mg mL1), has been among the most widely
studied proteins. It has very crucial role as a transporter of
a variety of fatty acids and capable of binding effectively with
metabolites and drug molecules, therefore governing the
distribution of such entities in plasma.44 The binding of
complexes 1–4 was investigated using native tryptophan emis-
sion quenching. The emission of HSA is mainly because of the
tryptophan residue (Trp-214) located in a hydrophobic envi-
Fig. 3 (a) UV-visible traces for [Eu(Anpp)(TTA)3] (20 mM) in 5 mM Tris ronment. Fig. 4 shows the quenching of emission intensity
buffer (pH 7.2) with increasing [CT-DNA] at 298 K; inset: [DNA]/D3af
along with hypsochromic shi upon gradual increasing
versus [DNA] plot for complex 1. (b) Emission spectral traces for EB-
bound CT-DNA with increasing concentration for complex 1 in 5 mM concentration of the complexes at lex ¼ 295 nm. The observed
Tris buffer (pH 7.2) 298 K; lex ¼ 546 nm, lem ¼ 603 nm, [DNA] ¼ spectral changes reveals that the binding of complexes leads to
212 mM, [EB] ¼ 12 mM; inset: a plot of I/I0 vs. [complex 1]. a change in the secondary structure of the protein through

Table 2 Binding parameter for the complexes 1–4 with CT-DNA and HSA

Complexes Kb/M1a (105) Kapp/M1b (107) KHSA/M1c (105) nd, K/M1e (105)

Complex 1 1.15  0.03 3.56 7.3  0.04 0.69, 2.5

Complex 2 8.8  0.07 3.77 6.5  0.02 0.72, 3.6
Complex 3 1.64  0.11 3.59 8.1  0.03 0.79, 9.3
Complex 4 3.68  0.10 3.65 7.1  0.03 0.71, 3.5
a
Kb: intrinsic DNA binding constant. b Kapp: apparent DNA binding constant. c
KHSA: Stern–Volmer quenching constant of HSA emission. d
n:
number of binding sites in protein. e K: HSA binding constant.

This journal is © The Royal Society of Chemistry 2017 RSC Adv., 2017, 7, 44272–44281 | 44275
 View Article Online

RSC Advances Paper

S17(b)–S19(b) in ESI†) showing quenching of emission intensity

by 35–40% with no apparent shi in emission maxima. It is
quite obvious from these results that the complexes are
affecting the microenvironments of both Tyr and Trp residues,
but the effect was much pronounced in microenvironment
around Trp.49

Photoactivated DNA cleavage activity

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Fig. 4 (a) The emission quenching of HSA on addition of complex 1 in

The DNA cleavage activity by photoactivation for the complexes
1–4 was carried out in 5 mM Tris HCl/NaCl buffer (pH ¼ 7.2)
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

5 mM Tris buffer (pH 7.2) at 298 K; inset: a plot of I0/I versus [complex
1]; lex ¼ 295 nm, lem ¼ 345 nm, [HSA] ¼ 5 mM. (b) Scatchard plot: log using supercoiled (SC) pUC19 DNA (30 mM, 0.2 mg) by exposing
[(I0 – I)/I] vs. log[complex] for HSA in the presence of complex 1. the sample to a radiation of 365 nm UV-A light by a low power
monochromatic lamp (6 W). The control experiment with only
SC-DNA did not displayed any noticeable photocleavage while
various hydrophobic interaction, electrostatic interaction, the ligands HTTA, Anpp and Pypp were showing 6, 9 and 15%
collisional quenching and ground state complex formation.45 cleavage of SC-DNA (Fig. 6, lanes 1–4). However EuCl3$6H2O
The dynamic quenching constant (KHSA) of the complexes were and TbCl3$6H2O were not showing any photocleavage (Fig. 6,
calculated from the slope of I0/I vs. [complex] linear plot using lanes 5, 6, 11–14). Complexes 2 and 4 displayed better photo-
Stern–Volmer equation (eqn (3)).46 The values of binding cleavage capability compared to 1 and 3 at 40 mM, mainly due to
constant (K) and the number of binding sites (n) was obtained the possible involvement of the pyrene ring. Treatment of SC-
from the linear log(I0/I  1) vs. log[complex] plot using Scatch- DNA with the complexes 1–4 in dark for 1.5 h did not show
ard equation (eqn (4)).47 The corresponding plots have been any apparent cleavage, rules out the possibility of any hydrolytic
shown in Fig. 4 and S14–S16 in ESI† and values are listed in cleavage by Ln(III) complexes.
Table 2. Obtained values of binding constant are of the order The groove binding nature of the complexes were also
105 M1 suggesting strong binding affinity of the complexes studied utilizing methyl green (MG), which is a major groove
towards target protein. binder of SC-DNA and showing 10% nicking of SC-DNA. All
the complexes bound with SC-DNA showed an inhibition of
their DNA photocleavage activity to its nicked circular form in
Synchronous uorescence studies
the presence of methyl green reveals the complexes 1–4 are the
Synchronous uorescence spectroscopy study provides crucial major groove binders (Fig. 6, lanes 15–19).23b
information in determining the molecular microenvironment The mechanism of DNA photocleavage activity of the
of chromophoric groups in protein cavity. As stated by Miller, complexes 1–4 was carried out in order to gain some insight into
change of Dl, which is the difference of emission and excitation the process of photocleavage using various additives like 1O2
wavelength (Dl ¼ lem  lex) gives the spectra of different nature. quenchers (L-Histidine, NaN3), cOH scavengers (DMSO, KI,
If Dl ¼ 60 nm, emission spectra will reect the characteristics of catalase).50–52 Photoinduced DNA cleavage reactions mainly
tryptophan (Trp) residue and Dl ¼ 15 nm will suggest the involve two ROS-mediated pathways: either via Type-II pathway
characteristics of tyrosine (Tyr) residue in HSA protein.48 The through 1O2 generation or via photoredox pathway that involves
synchronous spectra was recorded with increasing concentra- cOH generation. Addition of L-His and NaN3 to SC-DNA as 1O2
tion of complexes 1–4 both at Dl ¼ 60 nm and 15 nm. The quenchers, displayed partial inhibition of the photocleavage
uorescence spectra at Dl ¼ 60 nm in Fig. 5(a) and S17(a)– activity. Photocleavage of DNA by the complexes through 1O2
S19(a) in ESI† showing dramatic quenching of emission inten- was further conrmed by using D2O as solvent showing an
sity by 82–87% without any signicant changes in lem maxima. enhancement of the cleavage because of the longer lifetime of
Similarly, the synchronous spectra at Dl ¼ 15 nm (Fig. 5(b) and 1
O2 in D2O than in H2O.53 Addition of DMSO, KI and catalase as

Fig. 6 Photocleavage of SC pUC19DNA (30 mM, 0.2 mg) with

complexes 1–4 and controls (40 mM) in 50 mM Tris–HCl buffer (pH 7.2)
at 37  C for after 1.5 h exposure with UV-A light (l ¼ 365 nm, 6 W). L1:
DNA control; L2: DNA + HTTA; L3: DNA + Anpp; L4: DNA + Pypp; L5:
DNA + EuCl3$6H2O; L6: DNA + TbCl3$6H2O; L7: DNA + 1 (dark); L8:
DNA + 2 (dark); L9: DNA + 3 (dark); L10: DNA + 4 (dark); L11: DNA + 1;
Fig. 5 Synchronous emission spectra of HSA (5 mM) showing effect of L12: DNA + 2; L13: DNA + 3; L14: DNA + 4; L15: DNA + MG (methyl
increasing concentration of complex 1 (a) with Dl ¼ 60 nm and (b) with green); L16: DNA + MG + 1; L17: DNA + MG + 2; L18: DNA + MG + 3;
Dl ¼ 15 nm at 298 K in Tris–HCl buffer (pH ¼ 7.2). L19: DNA + MG + 4.

44276 | RSC Adv., 2017, 7, 44272–44281 This journal is © The Royal Society of Chemistry 2017
 View Article Online

Paper RSC Advances

triuoro acetylacetone, europium chloride hexahydrate and

terbium chloride hexahydrate were form Sigma Aldrich and
used without any further purication. Solvents purchased from
commercial sources were either of spectroscopic grade or
puried by standard literature procedures.54 Ln(TTA)3$2H2O
were prepared according to the literature reported procedure.55
Calf thymus (CT)-DNA, albumin from human serum (HSA),
agarose (molecular biology grade), methyl green, catalase, gel
loading solution and ethidium bromide were procured from
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

Sigma (U.S.A.). Milli-Q water (18.2 MU) was used to prepare

Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

Tris-(hydroxymethyl)-aminomethane–HCl (Tris–HCl) buffer

solution. Supercoiled (SC) pUC19 DNA was from Merck
Millipore (India).

General measurements
Perkin-Elmer Model 1320 FT-IR spectrometer was used for the
Fig. 7 Cleavage of SC pUC19 DNA (30 mM, 0.2 mg) by complexes 1 and
3 (40 mM) (wine) and (olive) on photo-exposure at 365 nm (6 W) for
infrared spectra with KBr disc in the operating range of 4000–
1.5 h in the presence of various additives in Tris–HCl/NaCl buffer. 400 cm1. WATERS Q-TOF Premier mass spectrometer was used
NaN3, 0.4 mM; KI, 0.4 mM; D2O, 16 mL; L-histidine, 0.4 mM; DMSO, for recording electrospray ionization mass spectral (ESI-MS)
4 mL; catalase, 4 U. measurements. 1H NMR spectra were recorded using JEOL-
ECX 500 FT (400 MHz) for the characterization of chalcones at
298 K with reference to TMS. UV-Vis spectra were recorded
hydroxyl radical scavengers showed partial inhibition of pho-
using Varian V670 spectrophotometer at 298 K.
tocleavage, suggesting the generation of cOH during the
Agilent Cary Eclipse uorescence spectrophotometer was
process. All the data shown in Fig. 7 and S22–S26 in ESI†
used for uorescence and time resolved luminescence spectra
conrms that photoinduced DNA cleavage here involves both
measurements. Luminescence decay measurements were done
Type-II and photoredox pathways and is consistent with earlier
with same instrument using a pulsed Xe-source at lex ¼ 340 nm
reported lanthanide complexes.23,24
and emission at 616 nm for Eu(III) and 545 nm for Tb(III)
complexes respectively. The decay curves were tted using
Conclusions nonlinear least square method. Calculation for determination
of number of H2O molecules coordinated to metal in the
Four new Eu(III) and Tb(III) complexes containing chalcones as
complexes 1–4 was done by the measurement of excited state
biologically diverse molecules and TTA as ancillary sensitizing
lifetimes in H2O and D2O and thereby applying modied Hor-
ligands have been designed, synthesized and characterized. The
rocks equations for ternary europium and terbium complexes
structurally characterized complex 3 showing an eight coordi-
respectively.39
nated square antiprismatic {EuN1O7} geometry. Strong lumi-
 
nescence from all the complexes suggest effective energy 1 1
qEu ¼ 1:2   0:25
transfer from sensitizing ligands to Ln(III). Horrock's experi- sH2 O sD2 O
ment showed the absence of any inner sphere H2O molecule (q <
1) attached to Ln(III) in solution. Complexes showed good  
binding affinity with DNA and HSA as evidenced form spectro- 1 1
qTb ¼ 5:0   0:06
scopic studies. Both the chalcone ligands containing pyrene or sH2 O sD2 O
anthracene acts as efficient photosensitizers to generate ROS for
DNA photocleavage. These complexes showed effective photo-
induced DNA cleavage under UV-A light of 365 nm at 40 mM
concentration through the generation of singlet oxygen (1O2) in Synthesis and characterization
a type-II pathway and cOH in a photoredox pathway. Further Synthesis of chalcones. To a mixture of acetyl pyridine
chalcone modications with a series of antenna moieties for the (0.60 g, 5 mmol) and 2-anthraldehyde (1.03 g, 5 mmol) or
development of highly emissive lanthanide chalcones 1-pyrene carbaldehyde (1.15 g, 5 mmol) was added an aqueous
complexes are in progress to study their various biological solution of 15% KOH (5 mL, 1.5 M). The reaction mixture was
potential utilizing lanthanide luminescence. stirred at RT for 24 h resulting in a yellow orange precipitate.
The precipitate was ltered, washed with cold ethanol (3 
Experimental section 5 mL) and dried in vacuum over P2O5. Precipitate obtained was
further recrystallized from ethanol to give the nal product
Materials (Scheme 2).34,35 The characterization data are given below:
Chemicals like 9-anthraldehyde, pyrene-1-carbaldehyde and 2- (E)-3-(Anthracen-9-yl)-1-(pyridin-2-yl)prop-2-en-1-one (Anpp).
acetyl pyridine were purchased from Alfa-Aesar. Theonyl Yield: 1.24 g (78%), UV-Vis (DMF): lmax (3/L mol1 cm1) ¼ 267

This journal is © The Royal Society of Chemistry 2017 RSC Adv., 2017, 7, 44272–44281 | 44277
 View Article Online

RSC Advances Paper

(93 800), 333 (10 800), 351 (19 600), 368 (27 000), 388 (26 900). Single crystal X-ray crystallography
FT-IR (in KBr/cm1): 3051 (br, aromatic C–H), 1670 (s, C]O),
[Eu(Pypp)(TTA)3] (3) was structurally characterized by single
1599 (s), 1582 (s), 1565 (s). 1H NMR (400 MHz, CDCl3, d from
crystal X-ray diffraction technique. A crystal of proper size was
TMS): 8.9 (d, 1H), 8.68 (1H, d), 8.48 (1H, s), 8.34 (2H, m), 8.29
mounted on a glass ber and used for collecting the data. X-ray
(1H, d; 1H, s), 8.03 (2H, m), 7.93 (2H, td), 7.5 (4H, m). ESI-MS
diffraction data were collected using u-scan technique (width of
(m/z): [M + H]+ calcd for C22H16N1O1, 310.123; found, 310.125.
0.5 per frame) at a scan rate of 10 s each frame on a Bruker D8
(E)-3-(Pyren-1-yl)-1-(pyridin-2-yl)prop-2-en-1-one (Pypp). Yield:
Quest microfocus X-ray CCD diffractometer with graphite
1.14 g (73%), UV-Vis (DMF): lmax (3/L mol1 cm1) ¼ 270 monochromated Mo Ka radiation (l ¼ 0.71073 Å) at 100(2) K
(91 000), 310 (59 600), 344 (45 300), 390 (70 300), 422 (69 800).
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

controlled by an APEX2 v2012.4-3 soware.56 Data were cor-

FT-IR (in KBr/cm1): 3044 (br, aromatic C–H), 1660 (s, C]O),
rected for Lorentz polarization correction thereaer processed
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

1588 (s), 1574 (s), 1560 (m). 1H NMR: (400 MHz, CDCl3, d from
with Bruker's SAINT soware which was collected using u–2q
TMS): 9.10 (1H, d), 8.78 (1H, s), 8.56 (3H, m), 8.18 (5H, m), 8.02
scan mode.57 Absorption corrections were applied on a SADABS
(2H, m), 7.90 (1H, s), 8.69 (1H, d), 7.51 (1H, s). ESI-MS (m/z): [M +
program to the collected reections and space group was
H]+ calcd for C24H16N1O1, 334.123; found, 334.124.
determined from XPREP.58 The structure solved on a SHELXL-
Synthesis of lanthanide complexes. To a solution of respec-
97 by direct methods, were rened using SHELXTL-6.14
tive Ln(TTA)3$2H2O (85.10 mg for Eu and 85.80 mg for Tb, 0.1 program on a F2 full-matrix least square method. Subse-
mmol) in THF (5 mL) was added a solution of chalcones quently obtained structure was rened on a SHEXTL-97 asso-
(37.21 mg for Anpp and 39.96 mg for Pypp, 0.12 mmol) and le
ciated to WinGX-1.70 crystallographic package.59–61 C38 atom in
on stirring for 12 h. The resulting solution was dried in vacuum
one TTA ligand having site occupancy factor (SOF) of 0.5 in the
and then redissolved in a minimum amount of THF. To this
asymmetric unit. A perspective view of the complex was ob-
solution an excess of hexane was added to precipitate out the
tained using ORTEP (Fig. 2) aer including all the hydrogen
nal product. The precipitate was ltered, washed with 5 mL
atoms in geometrically calculated positions rened with riding
diethyl ether and dried to give the desired product [Ln(Anpp)/
hydrogen model and all other non-hydrogen atoms were aniso-
(Pypp)(TTA)3] (1–4) in a good yield (Scheme 2). tropically rened.62 Selected bond length and bond angles are
[Eu(Anpp)(TTA)3] (1). Yield: 73.06 mg (65%). UV-Vis (DMF): shown in Table S1.† CCDC deposition number: CCDC 1566126.
lmax (3/L mol1 cm1) ¼ 270 (69 400), 346 (49 500). FT-IR (in
Crystallographic data for 3: C47.5H26.5Eu1F9N1O7S3, M ¼ 1142.34,
KBr/cm1): n ¼ 3432 (w, br, nO–H), 3053 (w), 2925 (w), 1601 , a ¼ 10.5489(9), b ¼ 10.8247(9), c ¼
triclinic, space group P1
(s, nC]O), 1537 (s), 1504 (m), 1464 (m), 1411 (s), 1356 (s), 1305
21.7672(19) Å, a ¼ 99.053(2), b ¼ 101.429(2), g ¼ 105.634(2) , V ¼
(s), 1247 (m), 1229 (s), 1186 (s), 1139 (s), 1059 (m), 933 (s), 892
2286.9(3) Å3, Z ¼ 2, Dx (g cm3) ¼ 1.659, T ¼ 100(2) K, q range ¼
(m), 858 (m), 786 (s, nCF3), 767 (s), 735 (s), 720 (s), 680 (m), 619
2.00–25.07 , m ¼ 1.598 mm1, F(000) ¼ 1133, reections collected
(s), 580 (s), 519 (w, nEu–N), 491 (w, nEu–O). ESI-MS (m/z): [M-TTA]+
¼ 45 431, unique reections ¼ 8100 (Rint ¼ 0.0588) Tmax/Tmin, ¼
calcd for C38H23N1O5F6S2Eu1, 904.013; found, 904.011. 0.7619/0.7406, data/restraints/parameters ¼ 8100/2/604, GOF on
[Tb(Anpp)(TTA)3] (2). Yield: 75.80 mg (67%). UV-Vis (DMF): F2 ¼ 1.109, R1 and wR2 [I > 2s(I)] ¼ 0.0663, 0.1726; 45 431
lmax (3/L mol1 cm1) ¼ 271 (69 000), 346 (42 700). FT-IR (in
collected reections, 8100 unique reections, Rint ¼ 0.0588, nal
KBr/cm1): n ¼ 3425 (w, br, nO–H), 3084 (w), 2963 (s), 1603 (s, nC]
R1 ¼ 0.0806 and wR2 ¼ 0.1867 (all data).
O), 1537 (s), 1502 (m), 1460 (m), 1412 (s), 1354 (s), 1305 (s), 1261
(s), 1229 (s), 1183 (s), 1098 (s), 1059 (s), 1020 (s), 932 (s), 877 (m),
858 (m), 799 (s, nCF3), 735 (s), 717 (s), 679 (s), 640 (s), 579 (s), 519 DNA binding experiments
(w, nTb–N), 486 (w, nTb–O). ESI-MS (m/z): [M-TTA]+ calcd for C38- Electronic absorption spectral studies. DNA binding studies
H23N1O5F6S2Tb1, 910.0175; found, 910.0154. were done by absorption spectral titration experiment in 5 mM
[Eu(Pypp)(TTA)3] (3). Yield: 68.90 mg (60%). UV-Vis (DMF): lmax Tris HCl-5 mM NaCl buffer (pH-7.2) using DMF solution of the
(3/L mol1 cm1) ¼ 273 (88 200), 344 (77 700), 440 (36 600). FT-IR complexes 1–4. An absorbance ratio (A260/A280) of 1.8–1.9 of calf
(in KBr/cm1): n ¼ 3432 (w, br, nO–H), 3091 (w), 2962 (s), 2925 (w), thymus DNA found in Tris HCl–NaCl buffer showing that there
1602 (vs., nC]O), 1536 (s), 1505 (m), 1459 (m), 1411 (s), 1353 (s), 1305 is hardly any scares of protein in DNA solution.63 The known
(s), 1261 (s), 1229 (s), 1185 (s), 1133 (s), 1092 (s) 1060 (m), 1025 (s), molar extinction coefficient (3260 ¼ 6600 M1 cm1) and the
933 (s), 845 (m), 799 (s, nCF3), 767 (s), 749 (s), 714 (s), 680 (m), 640 (s), absorbance recorded at 260 nm (A260) gave the concentration of
580 (s), 519 (w, nEu–N), 491 cm1 (w, nEu–O). ESI-MS (m/z): [M + Na]+ DNA.64 UV-Vis absorption spectral titrations were done by
calcd for C48H27N1O7F9S3Eu1Na1, 1171.991; found, 1171.970. varying DNA concentration while keeping the xed complex
[Tb(Pypp)(TTA)3] (4). Yield: 72.80 mg (63%). UV-Vis (DMF): concentration. The following eqn (1) was used to determine
lmax (3/L mol1 cm1) ¼ 273 (86 800), 344 (72 800), 440 (31 200). intrinsic binding constant (Kb) with ternary lanthanide
FT-IR (in KBr/cm1): n ¼ 3433 (w, br, nO–H), 3046 (w), 2963 (s), complexes.
2925 (w), 1602 (s, nC]O), 1535 (s), 1504 (m), 1464 (m), 1411 (s),
1353 (s), 1304 (s), 1261 (s), 1229 (s), 1184 (s), 1099 (s), 1061 (s), [DNA]/(3a  3f) ¼ [DNA]/(3b  3f) + 1/Kb(3b  3f) (1)
1023 (s), 932 (s), 844 (m), 799 (s, nCF3), 767 (s), 735 (s), 713 (s), 679
(m), 640 (s), 614 (s), 579 (s), 519 (w, nTb–N), 491 (w, nTb–O). ESI-MS where [DNA] is the concentration of DNA in base pairs and 3a is
(m/z): [M-TTA]+ calcd for C38H23N1O5F6S2Tb1, 934.0175; found, apparent molar absorptivity of the complexes while 3f and 3b are
934.0212. the molar absorptivity of the complexes in their free form and

44278 | RSC Adv., 2017, 7, 44272–44281 This journal is © The Royal Society of Chemistry 2017
 View Article Online

Paper RSC Advances

when completely bound to DNA.65 The DNA binding constant DNA photocleavage experiment. The cleavage of supercoiled
was obtained from slope to intercept ratio of the [DNA]/[3a  3f] (SC) pUC19 DNA (30 mM, 0.2 mg, 2686 base pairs) was done with
vs. [DNA] plot. photoinduced reactions by agarose gel electrophoresis in Tris
Competitive binding assay. Ethidium bromide (EB) acetate–EDTA (TAE) buffer (pH 8.1) at various concentration of
displacement assay used for estimation of competitive binding the complexes 1–4. The concentration of complexes 1–4 in DMF
with DNA and complexes were studied in Tris HCl–NaCl buffer or any other additive in buffer were reported only aer their
by recording the variation in the emission intensity of EB bound dilution to a nal volume of 20 mL by 50 mM Tris HCl buffer.
to DNA at 603 nm (lexc ¼ 546 nm). In comparison to the EB-DNA Aer an incubation for 1 h at 37  C, photoirradiation of the
adduct, the emission intensity of free form of EB is very less sample were carried out in dark using UV-A light of 365 nm
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

because of its quenching from the solvent molecule in buffer (6 W, Model VL-6.LC from Vilber Lourmat, France). Mechanistic
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

medium. The enhanced emission intensity of DNA bound EB study was carried out by taking various additives viz. DMSO,
was quenched upon addition of the complexes 1–4 and recor- NaN3, L-histidine, KI, catalase, D2O to DNA solution prior to
ded at increasing concentration of the complexes. The apparent addition of complexes. For studying effect of D2O, D2O itself was
binding constants of the complexes were calculated using the taken for the dilution of sample upto 20 mL. Aer photo-
following equation: irradiation of sample, a 3 mL of loading buffer consist of 0.25%
bromophenol, 0.25% xylene cyanol, 40% sucrose was mixed to
Kapp  C50 ¼ KEB  [EB] (2) it. Finally, the sample solution was loaded on a 1% agarose gel
containing 1 mg mL1 ethidium bromide and electrophoresis of
where Kapp stands for apparent binding constant of the
the sample was carried out in TAE buffer (pH-8.1) at 60 V for 2 h
complexes studied, C50 is the concentration of the complexes
in dark. UV-A light was used for visualization and images taken
added at which emission intensity reduces to 50% from EB–
with UVITEC FireReader V4 gel documentation system. The
DNA adduct, KEB is the binding constant of ethidium bromide cleavage products were quantied by measuring the intensity of
(KEB ¼ 1  107 M1) and [EB] is the concentration of the the band on a UVI band soware. The error observed was in the
ethidium bromide in buffer medium (12 mM).66
range of 4–6% in measuring the band intensities.
Protein binding experiments. Protein binding interaction
studies of the complexes 1–4 were carried out in 5 mM Tris HCl-
5 mM NaCl buffer (pH-7.2) using human serum albumin (HSA). Conflicts of interest
A stock solution of HSA was prepared in Tris buffer and its
concentration was calculated from known molar absorptivity There are no conicts to declare.
(3278 ¼ 44 000 dm3 mol1 cm1) and the recorded absorbance
(A278) at 278 nm.67,68 Aer taking a 1 mM solution of HSA, Acknowledgements
a quenching in emission intensity at 345 nm (lexc ¼ 295 nm) of
the tryptophan residue present in protein was recorded upon We thank IIT Kanpur for infrastructure and the Science and
increasing concentration of the complexes. The quenching Engineering Research Board (SERB) for nancial support (EMR/
constants were calculated using Stern–Volmer equation:46 2016/000521). ZA thanks to University Grants Commission
(UGC) and SD to Ministry of Human Resources and Develop-
I0/I ¼ 1 + KHSA[Q] (3) ment (MHRD) for the research fellowships.

where, I0 and I are the emission intensities of HSA in the

absence of a quencher and in the presence of a quencher of Notes and references
concentration [Q], gave the quenching constants (KHSA). Slope
of the plot I0/I vs. [Q] gave the value of KHSA. 1 S. Cotton, Lanthanides and actinide chemistry, John Wiley &
The values of binding constant (K) and number of binding Sons Ltd., England, 2006.
sites (n) was obtained from the linear log(I0/I  1) vs. log[Q] plot 2 (a) M. C. Hefferin, L. M. Matosziuk and T. J. Meade, Chem.
using Scatchard equation:47 Rev., 2014, 114, 4496–4539; (b) J. L. Major and T. J. Meade,
Acc. Chem. Res., 2009, 42, 893–903; (c) S. Shuvaev, M. Starck
log[(I0 – I)/I] ¼ log K + n log[Q] (4) and D. Parker, Chem.–Eur. J., 2017, 23, 9974–9989.
3 (a) P. Caravan, J. J. Ellison, T. J. McMurry and R. B. Lauffer,
Chem. Rev., 1999, 99, 2293–2352; (b) P. Caravan, Chem. Soc.
Synchronous uorescence spectroscopy. Synchronous emis- Rev., 2006, 35, 512–523; (c) M. Mikawa, H. Kato,
sion spectra were recorded to get insight into the binding M. Okumura, M. Narazaki, Y. Kanazawa, N. Miwa and
preference of the complexes 1–4 in different microenvironment H. Shinohara, Bioconjugate Chem., 2001, 12, 510–514.
of serum protein. This experiment was carried out by taking 4 (a) J.-C. G. Bünzli, Chem. Rev., 2010, 110, 2729–2755; (b)
1 mM concentration of HSA in Tris HCl–NaCl buffer with the S. V. Eliseeva and J.-C. G. Bünzli, Chem. Soc. Rev., 2010, 39,
addition of complex at Dl ¼ 15 nm corresponding to the tyro- 189–227.
sine residue and Dl ¼ 60 nm corresponding to tryptophan 5 (a) E. G. Moore, A. P. S. Samuel and K. N. Raymond, Acc.
residue of the serum protein. Chem. Res., 2009, 42, 542–552; (b) A. J. Amoroso and
S. J. A. Pope, Chem. Soc. Rev., 2015, 44, 4723–4742.

This journal is © The Royal Society of Chemistry 2017 RSC Adv., 2017, 7, 44272–44281 | 44279
 View Article Online

RSC Advances Paper

6 (a) S. Gai, C. Li, P. Yang and J. Lin, Chem. Rev., 2014, 114, 20 (a) D. A. Lutterman, P. K.-L. Fu and C. Turro, J. Am. Chem.
2343–2389; (b) H. Terraschke and C. Wickleder, Chem. Rev., Soc., 2006, 128, 738–739; (b) A. M. Angeles-Boza,
2015, 115, 11352–11378. H. T. Chifotides, J. D. Aguirre, A. Chouai, P. K.-L. Fu,
7 (a) J.-C. G. Bünzli and C. Piguet, Chem. Soc. Rev., 2005, 34, K. R. Dunbar and C. Turro, J. Med. Chem., 2006, 49, 6841–
1048–1077; (b) H. Tsukube and S. Shinoda, Chem. Rev., 6847.
2002, 102, 2389–2403; (c) H. Tsukube and S. Shinoda, 21 (a) K. Mitra, S. Gautam, P. Kondaiah and A. R. Chakravarty,
Analyst, 2011, 136, 431–435. Angew. Chem., Int. Ed., 2015, 54, 13989–13993; (b) W. Lu,
8 (a) L. V. Meyer, F. Schönfeld and K. M. Buschbaum, Chem. D. A. Vicic and J. K. Barton, Inorg. Chem., 2005, 44, 7970–7980.
Commun., 2014, 50, 8093–8108; (b) J. Heine and 22 (a) S. Swavey and K. J. Brewer, Inorg. Chem., 2002, 41, 6196–
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

K. M. Buschbaum, Chem. Soc. Rev., 2013, 42, 9232–9242; (c) 6198; (b) A. A. Holder, S. Swavey and K. J. Brewer, Inorg.
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

J. Rocha, L. D. Carlos, F. A. A. Paz and D. Ananias, Chem. Chem., 2004, 43, 303–308.
Soc. Rev., 2011, 40, 926–940. 23 (a) A. Hussain, D. Lahiri, M. S. A. Begum, S. Saha,
9 (a) S. M. Larson, J. A. Carrasquillo, N.-K. V. Cheung and R. Majumdar, R. R. Dighe and A. R. Chakravarty, Inorg.
O. W. Press, Nat. Rev. Cancer, 2015, 15, 347–360; (b) Chem., 2010, 49, 4036–4045; (b) A. Hussain, S. Gadadhar,
R. D. Teo, J. Termini and H. B. Gray, J. Med. Chem., 2016, T. K. Goswami, A. A. Karande and A. R. Chakravarty, Eur. J.
59, 6012–6024. Med. Chem., 2012, 50, 319–331; (c) A. Hussain, K. Somyajit,
10 (a) M. D. Gross, G. L. Nelsestuen and R. Kumar, J. Biol. B. Banik, S. Banerjee, G. Nagaraju and A. R. Chakravarty,
Chem., 1987, 262, 6539–6545; (b) J. M. Harroweld, Dalton Trans., 2013, 42, 182–195.
M. I. Ogden, W. R. Richmond and A. H. Whit, J. Chem. 24 (a) S. Dasari and A. K. Patra, Dalton Trans., 2015, 44, 19844–
Soc., Dalton Trans., 1991, 2153–2160. 19855; (b) S. Dasari, S. Singh, S. Sivakumar and A. K. Patra,
11 (a) S. P. Fricker, Chem. Soc. Rev., 2006, 35, 524–533; (b) Chem.–Eur. J., 2016, 22, 17387–17396; (c) A. Chandra,
K. Wang, R. Li, Y. Cheng and B. Zhu, Coord. Chem. Rev., K. Singh, S. Singh, S. Sivakumar and A. K. Patra, Dalton
1999, 190–192, 297–308. Trans., 2016, 45, 494–497; (d) K. Singh, S. Singh,
12 (a) M. Bottrill, L. Kwok and N. J. Long, Chem. Soc. Rev., 2006, P. Srivastava, S. Sivakumar and A. K. Patra, Chem.
35, 557–571; (b) P. Hermann, J. Kotek, V. KubÍček and Commun., 2017, 53, 6144–6147.
I. Lukeš, Dalton Trans., 2008, 23, 3027–3047. 25 M. Sy, A. Nonat, N. Hildebrandt and L. J. Charbonnihre,
13 R. Bonnett, Chemical Aspects of Photodynamic Therapy, Chem. Commun., 2016, 52, 5080–5095.
Gordon & Breac, London, UK, 2000. 26 (a) V. Divya, M. L. P. Reddy and R. Pavithran, Dalton Trans.,
14 (a) D. E. J. G. J. Dolmans, D. Fukumura and R. K. Jain, Nat. 2013, 42, 15249–15262; (b) D. B. A. Raj, S. Biju and
Rev. Cancer, 2003, 23, 380–387; (b) J. L. Sessler and M. L. P. Reddy, Inorg. Chem., 2008, 47, 8091–8100; (c)
R. A. Miller, Biochem. Pharmacol., 2000, 59, 733–739; (c) P. Martı́n-Ramos, C. Coya, Á. L. Álvarez, M. R. Silva,
G. Thiabaud, R. McCall, G. He, J. F. Arambula, Z. H. Siddik C. Zaldo, J. A. Paixao, P. Chamorro-Posada and J. Martı́n-
and J. L. Sessler, Angew. Chem., Int. Ed., 2016, 55, 12626– Gil, J. Phys. Chem. C, 2013, 117, 10020–10030; (d) J. Shi,
12631. Y. Hou, W. Chu, X. Shi, H. Gu, B. Wang and Z. Sun, Inorg.
15 (a) M. Ethirajan, Y. Chen, P. Joshi and R. K. Pandey, Chem. Chem., 2013, 52, 5013–5022.
Soc. Rev., 2011, 40, 340–362; (b) M. R. Detty, S. L. Gibson 27 (a) J. Yu, L. Zhou, H. Zhang, Y. Zheng, H. Li, R. Deng, Z. Peng
and S. J. Wagner, J. Med. Chem., 2004, 47, 3897–3915; (c) and Z. Li, Inorg. Chem., 2005, 44, 1611–1618; (b) Y. Zheng,
M. Triesscheijn, P. Baas, J. H. M. Schellens and J. Lin, Y. Liang, Q. Lin, Y. Yu, Q. Meng, Y. Zhou, S. Wang,
F. A. Stewart, Oncologist, 2006, 11, 1034–1044. H. Wang and H. Zhang, J. Mater. Chem., 2001, 11, 2615–2619.
16 (a) J. P. Celli, B. Q. Spring, I. Rizvi, C. L. Evans, K. L. Samkoe, 28 C. Zhuang, W. Zhang, C. Sheng, W. Zhang, C. Xing and
S. Verma, B. W. Pogue and T. Hasan, Chem. Rev., 2010, 110, Z. Miao, Chem. Rev., 2017, 117, 7762–7810.
2795–2838; (b) K. Szaciłowski, W. Macyk, A. D. Matuszek, 29 (a) J. Li, D. Li, Y. Xu, Z. Guo, X. Liu, H. Yang, L. Wu and
M. Brindell and M. Stochel, Chem. Rev., 2005, 105, 2647– L. Wang, Bioorg. Med. Chem. Lett., 2017, 27, 602–606; (b)
2694. Z. Liu, L. Tang, P. Zou, Y. Zhang, Z. Wang, Q. Fang,
17 (a) S. I. Moriwaki, J. Misawa, Y. Yoshinari, I. Yamada, L. Jiang, G. Chen, Z. Xu, H. Zhang and G. Liang, Eur. J.
M. Takigawa and Y. Tokura, Photodermatol., Photoimmunol. Med. Chem., 2014, 74, 671–682.
Photomed., 2001, 17, 241–243; (b) M. Ochsner, J. Photochem. 30 (a) N. J. Lawrence, R. P. Patterson, L.-L. Ooi, D. Cook and
Photobiol., B, 1996, 32, 3–9. S. Ducki, Bioorg. Med. Chem. Lett., 2006, 16, 5844–5848; (b)
18 R. R. Allison and C. H. Sibata, Photodiagn. Photodyn. Ther., N. Mateeva, S. V. K. Eyunni, K. K. Redda, U. Ononuju,
2010, 7, 61–75. T. D. Hansberry, C. Aikens and A. Nag, Bioorg. Med. Chem.
19 (a) F. S. Mackay, J. A. Woods, P. Heringová, J. Kaspárková, Lett., 2017, 27, 2350–2356.
A. M. Pizarro, S. A. Moggach, S. Parsons, V. Brabec and 31 (a) M. Liu, P. Wilairat and M. L. Go, J. Med. Chem., 2001, 44,
P. J. Sadler, Proc. Natl. Acad. Sci. U. S. A., 2007, 104, 20743– 4443–4452; (b) J. N. Dominguez, C. Leon, J. Rodrigues,
20748; (b) N. J. Farrer, J. A. Woods, L. Salassa, Y. Zhao, N. Gamboa de Dominguez, J. Gut and P. J. Rosenthal,
K. S. Robinson, G. Clarkson, F. S. Mackay and P. J. Sadler, J. Med. Chem., 2005, 48, 3654–3658.
Angew. Chem., Int. Ed., 2010, 49, 8905–8908; (c) N. J. Farrer, 32 P. M. Sivakumar, T. M. Kumar and M. Doble, Chem. Biol.
L. Salassa and P. J. Sadler, Dalton Trans., 2009, 10690–10701. Drug Des., 2009, 74, 68–79.

44280 | RSC Adv., 2017, 7, 44272–44281 This journal is © The Royal Society of Chemistry 2017
 View Article Online

Paper RSC Advances

33 (a) S. Shettigar, K. Chandrasekharan, G. Umesh, 46 J. R. Lakowicz, Principles of Fluorescence Spectroscopy,

B. K. Sarojini and B. Narayana, Polymer, 2006, 47, 3565– Springer, New York, 3rd edn, 2006.
3567; (b) Y. J. Jung, K.-I. Son, Y. E. Oh and D.-Y. Noh, 47 G. Scatchard, Ann. N. Y. Acad. Sci., 1949, 51, 660–672.
Polyhedron, 2008, 27, 861–867. 48 (a) J. Tang, F. Luan and X. Chen, Bioorg. Med. Chem., 2006,
34 (a) P. M. Gallego, H. D. Dulk, J. Brouwer, H. Kooijman, 14, 3210–3217; (b) J. N. Miller, Proc. Anal. Div. Chem. Soc.,
A. L. Spek, O. Roubeau, S. J. Teat and J. Reedijk, Inorg. 1979, 16, 203–208.
Chem., 2008, 47, 11171–11179; (b) B. Song, G. Wang, 49 N. Selvakumaran, N. S. P. Bhuvanesh, A. Endo and
M. Tan and J. Yuan, J. Am. Chem. Soc., 2006, 128, 13442– R. Karvembu, Polyhedron, 2014, 14, 95–109.
13450. 50 M. Y. Li, C. S. Cline, E. B. Koker, H. H. Carmichael,
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

35 (a) M. Chhatwal, A. Kumar, R. D. Gupta and S. K. Awasthi, C. F. Chignell and P. Bilski, Photochem. Photobiol., 2001,
Open Access Article. Published on 13 September 2017. Downloaded on 15/09/2017 05:12:07.

RSC Adv., 2015, 5, 51678–51681; (b) K. C. Rout and 74, 760–764.

B. Mondal, Inorg. Chim. Acta, 2015, 437, 54–58. 51 S. M. Klein, G. Cohen and A. I. Cederbaum, Biochemistry,
36 (a) J. Yu, L. Zhou, H. Zhang, Y. Zheng, H. Li, R. Deng, Z. Peng 1981, 20, 6006–6012.
and Z. Li, Inorg. Chem., 2005, 44, 1611–1618; (b) J. Li, H. Li, 52 J. S. Beckman, T. W. Beckman, J. Chen, P. A. Marshall and
P. Yan, P. Chen, G. Hou and G. Li, Inorg. Chem., 2012, 51, B. A. Freeman, Proc. Natl. Acad. Sci. U. S. A., 1990, 87,
5050–5057; (c) J. Sun, B. Song, Z. Ye and J. Yuan, Inorg. 1620–1624.
Chem., 2015, 54, 11660–11668; (d) J. Shi, Y. Hou, W. Chu, 53 (a) A. U. Khan, J. Phys. Chem., 1976, 80, 2219–2228; (b)
X. Shi, H. Gu, B. Wang and Z. Sun, Inorg. Chem., 2013, 52, P. B. Merkel and D. R. Kearns, J. Am. Chem. Soc., 1972, 94,
5013–5022. 1029–1030.
37 P. Martı́n-Ramos, C. Coya, Á. L. Álvarez, M. R. Silva, C. Zaldo, 54 D. D. Perrin, W. L. F. Armarego and D. R. Perrin, Purication
J. A. Paixão, P. Chamorro-Posada and J. MartÍn-Gil, J. Phys. of Laboratory Chemicals, Pergamon Press, Oxford, 1980.
Chem. C, 2013, 117, 10020–10030. 55 L. R. Melby, N. J. Rose, E. Abramson and J. C. Caris, J. Am.
38 (a) P. Lenaerts, K. Driesen, R. V. Deun and K. Binnemans, Chem. Soc., 1964, 86, 5117–5125.
Chem. Mater., 2005, 17, 2148–2154; (b) P. Lenaerts, 56 APEX2 v2012.4, Bruker AXS, Madison, WI, 1999.
E. Ryckebosch, K. Driesen, R. V. Deun, P. Nockemann, 57 N. Walker and D. Stuart, Acta Crystallogr., Sect. A: Found.
C. G. Walrand and K. Binnemans, J. Lumin., 2005, 114, 77– Crystallogr., 1983, 39, 158–166.
84; (c) R.-J. Zhang, K.-Z. Yang, A.-C. Yub and X.-S. Zhao, 58 G. M. Sheldrick, SADABS, Area Detector Absorption Correction,
Thin Solid Films, 2000, 363, 275–278. University of Göttingen, Göttingen, Germany, 2001.
39 (a) W. D. Horrocks Jr and D. R. Sudnick, J. Am. Chem. Soc., 59 G. M. Sheldrick, SHELX-97, Program for Renement of Crystal
1979, 101, 334–340; (b) A. Beeby, I. M. Clarkson, Structures, University of Göttingen, Göttingen, Germany,
R. S. Dickins, S. Faulkner, D. Parker, L. Royle, A. S. de 1997.
Sousa, J. A. G. Williams and M. Woods, J. Chem. Soc., 60 (a) G. M. Sheldrick, Acta Crystallogr., Sect. A: Found.
Perkin Trans. 1, 1999, 493–504. Crystallogr., 2008, 64, 112–122; (b) G. M. Sheldrick,
40 (a) E. C. Long and J. K. Barton, Acc. Chem. Res., 1990, 23, 271– SHELXTL 6.14, Bruker, AXS Inc., Madison, WI, 2000.
273; (b) A. C. Komor and J. K. Barton, Chem. Commun., 2013, 61 (a) L. J. Farrugia, WINGX ver 1.70, An Integrated System of
49, 3617–3630. Windows Programs for the Solution, Renement, and Analysis
41 (a) T. M. Kelly, A. B. Tossi, D. J. McConnell and T. C. Strekas, of Single Crystal X-ray Diffraction Data, Department of
Nucleic Acids Res., 1985, 13, 6017–6034; (b) V. A. Bloomeld, Chemistry, University of Glasgow, 2005; (b) L. J. Farrugia,
D. M. Crothers and I. Tinocoo Jr, Physical Chemistry of J. Appl. Crystallogr., 1999, 32, 837–838.
Nucleic Acids, Harper & Row, New York, 1974, p. 432; (c) 62 M. N. Burnett and C. K. Johnson, ORTEP-III, Report ORNL–
J. B. Chaires, Curr. Opin. Struct. Biol., 1998, 8, 314–320. 6895, Oak Ridge National Laboratory, Oak Ridge, TN, 1996.
42 (a) J. Olmsted III and D. R. Kearns, Biochemistry, 1977, 16, 63 J. Marmur, J. Mol. Biol., 1961, 3, 208–218.
3647–3754; (b) D. L. Boger, B. E. Fink, S. R. Brunnette, 64 M. E. Reichmann, S. A. Rice, C. A. Thomas and P. Doty, J.
W. C. Tse and M. P. Hedrick, J. Am. Chem. Soc., 2001, 123, Am. Chem. Soc., 1954, 76, 3047–3053.
5878–5891. 65 A. Wolfe, G. H. Shimer and T. Meehan, Biochemistry, 1987,
43 (a) M. J. Waring, J. Mol. Biol., 1965, 13, 269–282; (b) 26, 6392–6396.
B. C. Baguley and E.-M. Falkenhaug, Nucleic Acids Res., 66 M. Lee, A. L. Rhodes, M. D. Wyatt, S. Forrow and J. Hartley,
1978, 5, 161–171. Biochemistry, 1993, 32, 4237–4245.
44 (a) S. Curry, H. Mandelkow, P. Brick and N. Franks, Nat. 67 T. Peters Jr, All About Albumin: Biochemistry, Genetics and
Struct. Biol., 1998, 5, 827–835; (b) J. Ghuman, Medical Applications, Academic Press, New York, 1995.
P. A. Zunszain, I. Petitpas, A. A. Bhattacharya, M. Otagiri 68 E. Alarcon, A. Aspee, M. Gonzalez-Bejar, A. M. Edwards,
and S. Curry, J. Mol. Biol., 2005, 353, 38–52. E. Lissi and J. C. Scaiano, Photochem. Photobiol. Sci., 2010,
45 (a) T. Peters, Adv. Protein Chem., 1985, 37, 161–245; (b) 9, 455–461.
Y.-Q. Wang, H.-M. Zhang, G.-C. Zhang, W.-H. Tao and
S.-H. Tang, J. Lumin., 2007, 126, 211–218.

This journal is © The Royal Society of Chemistry 2017 RSC Adv., 2017, 7, 44272–44281 | 44281