Liquid crystalline cholesterol-based ortho-palladated curcumin complexes as multifunctional biomaterials

Article abstract of DOI:10.1080/15421400701833981

Mononuclear ortho-palladated complexes containing 2-phenylquinoline ligand functionalized with a chiral entity and a biologically active O,O chelated ligand have been synthesized and fully characterized. The evaluation of the liquid crystalline properties

Full text of DOI:10.1080/15421400701833981

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Liquid Crystalline Cholesterol-
Based Ortho-Palladated
Curcumin Complexes as
Multifunctional Biomaterials
Daniela Pucci a , Rossana Bloise a , Anna Bellusci a
, Sergio Bernardini b , Mauro Ghedini a , Alessandra
Valentini b & Alessandra Crispini a
a Centro di Eccellenza CEMIF.CAL-LASCAMM, CR-
INSTM Unità della Calabria, Dipartimento di
Chimica , Università della Calabria , Italy
b Department of Internal Medicine and Department
of Laboratory Medicine-PTV , Università di Roma Tor
Vergata; Bambino-Gesù Children's Hospital-IRCCS
Roma , Italy
Published online: 22 Sep 2010.
To cite this article: Daniela Pucci , Rossana Bloise , Anna Bellusci , Sergio
Bernardini , Mauro Ghedini , Alessandra Valentini & Alessandra Crispini (2008)
Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin Complexes as
Multifunctional Biomaterials, Molecular Crystals and Liquid Crystals, 481:1, 14-25,
DOI: 10.1080/15421400701833981
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Mol. Cryst. Liq. Cryst., Vol. 481, pp. 14–25, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400701833981
Liquid Crystalline Cholesterol-Based Ortho-Palladated
Curcumin Complexes as Multifunctional Biomaterials
Daniela Pucci1, Rossana Bloise1, Anna Bellusci1,
Sergio Bernardini2, Mauro Ghedini1, Alessandra
Valentini2, and Alessandra Crispini1
1
`
Centro di Eccellenza CEMIF.CAL-LASCAMM, CR-INSTM Unita della
`
Calabria, Dipartimento di Chimica, Universita della Calabria, Italy
2Department of Internal Medicine and Department of Laboratory
`
`
Medicine-PTV, Universita di Roma Tor Vergata; Bambino-Gesu
Children’s Hospital-IRCCS Roma, Italy
Mononuclear ortho-palladated complexes containing 2-phenylquinoline ligand func-
tionalized with a chiral entity and a biologically active O,O chelated ligand have been
synthesized and fully characterized. The evaluation of the liquid crystalline properties
of these non-conventional compounds is reported in view of a potential use of these
organometallic systems in generating new bifunctional biomaterials.
Keywords: chirality; curcumin; cyclopalladated 2-phenylquinoline complexes; tropolone
INTRODUCTION
Despite of the fact that thousands of metal-complexes have been
produced since the discovery of the anticancer activity of cis-platin and
its analogues, there is a growing involvement on the design of new
coordination compounds that will combat intrinsic and acquired drug
resistance and that will reduce the toxic side effects of the chemioterapy.
In particular, the success of organo-transition metal compounds in
combating cancer has increased the interest in the synthesis of
pharmaceuticals based on organometallic compounds. Cyclopalladated
`
This work was partly supported by both the Ministero dell’Istruzione, dell’Universita
e della Ricerca through the Centro di Eccellenza CEMIF.CAL grant and Progetto Prosica
POR Calabria (Misura 316. A.3) grant.
Address correspondence to Daniela Pucci, Centro di Eccellenza CEMIF.CAL -
`
LASCAMM, CR-INSTM Unita della Calabria, Dipartimento di Chimica, Universita della
Calabria, Arcavacata (CS) 1-87036, Italy. E-mail: d.pucci@unical.it
14

Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin
15
complexes are promising antitumor drugs effective both in vitro and in
vivo, when compared to many platinum-based anticancer compounds [1].
Our experience in cyclopalladation in the field of liquid crystals [2]
and most recently in ortho-palladation to produce antitumor agents
[3,4] encouraged the design of a new cyclometallating ligand, based on
the bioactive 2-phenylquinoline framework on which a cholesteryl ester
unit has been introduced as chiral terminal substituent. The promeso-
genic cholesterol unit has been choosen for its universal affinity for cell
membranes, the ability to self order into liquid crystalline state and
because its use into liposomes has been shown to reduce significantly
leakage of the encapsulated drug during circulation in the extracellular
moiety [5]. In particular we have investigated the cyclopalladating
ability of this ligand by synthetizing the corresponding dinuclear
cyclopalladated complex which is the first step towards the design of
hybrid species, combining in a single molecule two bioactive chelated
functional moieties. Indeed, the 2-phenylquinoline cyclopalladated
fragment has been conjugated to a ligand of established effectiveness
in combating cancer, the curcumin (1,7-bis(4-hydroxy-3-methoxyphe-
nyl)-1,6- heptadiene-3,5-dione, diferuloyl methane), curc, and to a newly
synthetized alkoxy curcumin derivative, in which a long alkyl chain
has been grafted onto the 4 position of the aromatic ring, curc22. We
envisaged the possibility of using such systems to design amphiphilic
metallomesogens in order to get multifunctional biomaterials bearing
at the same time the active principe and the delivery component, becom-
ing innovative tools in establishing new and effective therapies.
Herein we report the synthesis and the thermal characterization of
the new functionalized 2-phenylquinoline ligand HL obtained introdu-
cing a cholesteryl ester unit as chiral chain, and of a series of deriva-
tives containing O,O chelating bioactive ligands (O,O ¼ monoanionic
form of tropolone, curcumin and its newly synthetized alkoxy deriva-
tive, curc22), of general formula [(L)Pd(O,O)] (Scheme 1). The thermal
behaviour of the obtained complexes has been investigated revealing
the formation of liquid crystals with different mesophase organiza-
tions depending on the shape of the molecule. Moreover, we have
performed also preliminary biological studies on the same cancer cell
line tested on the analogous curcumin derivatives [4] and the results
are herein reported.
EXPERIMENTAL SECTION
Measurements
The 1H NMR spectra were recorded on a Bruker Avance AC-300
spectrometer in CDCl3 solution, using tetramethylsilane (TMS) as

16
D. Pucci et al.
SCHEME 1 Synthetic route to HL and the corrisponding [(L)Pd(O,O)]
complexes.
internal standard. Elemental analyses (CHN) were performed with a
Perkin Elmer 2400 microanalyzer by the Microanalytical Laboratory
at the University of Calabria. Infrared spectra (KBr) were recorded
on a Perkin Elmer Spectrum One spectrometer. The textures of the
mesophases were studied with a Leica DMLP polarizing microscope
equipped with a CaLCTec heating stage. The transition temperatures
were measured on a Perkin Elmer DSC 7 Differential Scanning
Calorimeter with a heating and cooling rate of 10ꢀC=min. The instru-
ment was calibrated with Indium.

Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin
17
Synthesis
2-Phenyl-4-quinoline-carboxylic acid was purchased from Aldrich and
used without purification, while the curcumin, purchased from
Aldrich, was used after separation into individual components as
previously reported [4]. Curc22 compound was prepared as described
in the literature [4]. The potassium tropolonato salt was prepared
stirring the tropolone in a basic solution of EtOH with a stoichiometric
rate of KOH.
Synthesis of Cholesteryl-2-phenylquinoline-4-carboxylate, HL
To 2-phenyl-4-quinoline carboxilic acid (2 g, 8.02 mmol), under
nitrogen atmosphere, was added SOCl2 (10 mL) and the mixture was
stirred at 80ꢀC for 24 h. The solvent and the excess of SOCl2 were
removed under vacuum and the chloride of the 2-phenyl-4-quinoline
carboxilic acid (2.10 g, 8.02 mmol) was immediately reacted with a
solution of cholesterol (3.71 g, 9.6 mmol) in 50 mL of toluene. The
mixture was stirred at 0ꢀC, under nitrogen atmosphere, over a period
of 30 min and then at 110ꢀC for 48 h. The solvent was removed under
vacuum and the remaining residue was extracted with a basic solution
of NaHCO3. After crystallization from methanol (ꢁ20ꢀC), the pure
white solid L was obtained. Yield: 85%. Anal. Calcd for C43H55NO2
(Mw ¼ 617.91): C 83.58 H 8.97 N 2.26. Found C 83.07 H 9.23 N
2.66%. 1H-NMR (300 MHz, CDCl3): d 8.71 (d, J ¼ 7.59 Hz, H1),
8.35 (s, H5), 8.21 (m, 3H, H6,10,4), 7.76 (t, J ¼ 5.47 Hz, H3), 7.62
(t, J ¼ 5.57 Hz, H2), 7.53 (m, 3H, H7, 8, 9), 5.48 (d, J ¼ 3.9 Hz, Hc),
0
5.05 (m, 1H, Ha), 2.58 (d, 2H, J ¼ 7.81 Hz, Hb,b ), 0.70–2.09 (m, 41H,
CꢁH). IR (KBr, n=cmꢁ1): 2941-2866 (CꢁH), 1713 (CꢁOOR).
Synthesis of [(L)Pd(l-OAc)]2
To a solution of HL (0.5 g, 0.809 mmol) in 15 mL of acetic acid was
added palladium (II) acetato (0.181 g, 0.809 mmol) at 60ꢀC, under
nitrogen atmosphere, and immediatly a red precipitate was obtained.
The resulting suspension was stirred over a period of 12 h. The
product was filtered, washed with EtOH and recrystallized from
MeOH (ꢁ20ꢀC). Yield: 90%. Anal. Calcd for C90H114O8N2Pd2 (Mw ¼
1564.85): C 69.07 H 7.34 N 1.79. Found C 69.12 H 7.75 N 1.89%.
1H-NMR (300 MHz, CDCl3): d 8.54 (d, J ¼ 6.71 Hz, 2H, H1trans), 8.49
(d, 2H, H1cis), 8.24 (d, J ¼ 7.33 Hz, 2H, H7trans), 8.12 (d,2H, H7cis),
7.71 (s, 2H, H5trans), 7.50 (m, 2H, H8trans), 7.42 (m, 2H, H9trans), 7.18
(m, 2H, H8cis), 7.08 (m, 2H, H9cis), 6.85 (d, J ¼ 7.94 Hz, 2H, H4cis),
6.80 (d, 2H, H4trans), 6.70 (m, 4H, H3,10cis), 6.62 (t, 2H, H2cis), 6.53

18
D. Pucci et al.
(m, 2H, H3trans) 6.46 (t, J ¼ 5.49 Hz, 2H, H10trans), 6.22 (m, 2H, H2trans),
5.54 (d, J ¼ 7.32 Hz, Hc trans), 5.49 (d, 2H, Hc cis), 5.09 (m, 2H, Ha trans),
0
5.02 (m, 2H, Hacis), 2.66 (d, 2H, J ¼ 10.6 Hz, Hb,b trans), 2.60 (d, 2H,
Hb,b cis), 0.70–2.39 (m, 41H, CꢁH). IR (KBr, n=cmꢁ1): 2934-2865
0
(CꢁH), 1726 (CꢁO), 1570 (CꢁO acetato).
Synthesis of [(L)Pd(trop)], 1
Ktrop (0.030 g, 0.191 mmol), was added to a solution of [(L)Pd(m-
OAc)]2, 1 (0.15 g, 0.095 mmol), in 15 mL of CH2Cl2. The resulting red
solution that was stirred for 4 days at room temperature, became
yellow. This solution was filtered, concentrate evaporating the solvent
and recrystallized from EtOH (ꢁ20ꢀC). Yield 85%. Anal. Calcd for
C50H60O4NPd (Mw ¼ 845.44): C 71.03 H 7.15 N 1.65. Found C 71.25
1
H 6.98 N 1.51%. H-NMR (300 MHz CDCl3): d 9.47 (d, J ¼ 8.48 Hz,
H1), 8.65 (d, 1H, J ¼ 7.36 Hz, H4), 8.17 (s, 1H, H5), 7.87 (t, 1H,
J ¼ 5.52, H8), 7.75 (d, 1H, J ¼ 8.93 Hz, H10) 7.63 (t, 1H, J ¼ 7.25 Hz
0
0
H9), 7.56 (d, 1H, J ¼ 9.14 Hz, H7) 7.39 (m, 4H, Ha0;a0 ;b0;b0 ), 7.20 (m,
0
2H, H2,3), 6.93 (m, 1H,Hc ), 5.50 (d, J ¼ 3.9 Hz, Hc), 5.05 (m, 1H, Ha),
0
2.58 (d, 2H, J ¼ 7.80 Hz, Hb,b ), 0.69–2.13 (m, 41H, CꢁH). IR (KBr,
n=cmꢁ1): 2945-2865 (CꢁH), 1721 (CꢁO), 1592 (CꢁC trop).
Synthesis of [(L)Pd(curc)], 2
A suspension of [(L)Pd(m-OAc)]2, 1 (0.15 g, 0.095 mmol) in 10 mL of
MeOH was reacted with a solution of pure curcumin (0.070 g,
0.191 mmol) in 10 mL of MeOH. The resulting red mixture, that
became yellow, was stirred at room temperature for 48 h. The yellow
solid was filtered and recrystallized from MeOH. Yield 70%. Anal.
Calcd for C64H74O8NPd þ 2 H2O (Mw ¼ 1127.74): C 68.16 H 6.97 N
1.24. Found C 68.61 H 6.89 N 1.52%. 1H-NMR (300 MHz CDCl3):
d 9.67 (d, 1H, J ¼ 8,54 Hz, H1), 8.65 (d, 1H, J ¼ 8.55 Hz, H4), 8.22 (s,
0
1H, H5), 7.85 (m, 2H, H8,9), 7.60 (m, 4H, H3;7;d0;d0 ), 7.25 (m, 2H,
0
0
0
H
2,10), 7.10 (m, 4H, He0;e0 ;g0;g0 ), 6.93 (d, 2H, J ¼ 8.85 Hz, Hf0f0 ), 6.60
0
0
0
0
(d, 2H, J ¼ 15.56 Hz, Hc c ), 5.79 (s, 2H, OHcurc), 5.72 (s, 1H, Hb ),
5.49 (d, J ¼ 3.9 Hz, Hc), 5.05 (m, 1H, Ha), 3.95 (s, 6H, OCH3), 2.60
(d, 2H, J ¼ 7.80 Hz, Hb,b ), 0.70–2.25 (m, 41H, CꢁH). IR (KBr, n=cmꢁ1):
0
1): 2948 (CꢁH), 1721 (CꢁO), 1626 (C–Ocurc), 1508 (CꢁC).
Synthesis of [(L)Pd(curc22)], 3
To a solution of curc22 (0.063 g, 0.063 mmol) in 15 mL of CHCl3 was
added the binuclear precursor [(L)Pd(m-OAc)]2, 1 (0.050 g, 0.031 mmol).

Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin
19
The resulting orange solution was stirred for 3 days at room
temperature. The yellow solid that was obtained was filtered and
recrystallized from EtO2. Yield: 75%. Anal. Calcd for C108H161O8-
NPd þ 3H2O (Mw ¼ 1761.90): C 73.62 H 9.55 N 0.79. Found C 73.66
H 9.65 N 0.95%. 1HꢁNMR (300 MHz CDCl3): d 9.67 (d, 1H,
J ¼ 9.00 Hz, H1), 8.66 (d, 1H, J ¼ 9.00 Hz, H4), 8.27 (s, 1H, H5),
0
0
7.88 (m, 2H, H8,9), 7.64 (m, 4H, H3;7;d ;d0 ), 7.25 (m, 2H, H2,10), 7.13
0
0
0
(m, 4H, Hg0;g0 e0;e0 ), 6.99 (d, 2H, J ¼ 7,70 Hz, Hf0;f0 ), 6.65 (d, 2H,
0
J ¼ 15.11 Hz, Hc0;c0 ), 5.75 (s, 1H, Hb), 5.50 (d, J ¼ 3.9 Hz, Hc), 5.05
(m, 1H, Ha), 4.05 (d, 4H, OCH2(CH2)20CH3), 3.93 (s, 6H, OCH3curc),
0
2.59 (d, 2H, J ¼ 7.80 Hz, Hb,b ), 0.70–2.01 (m, 41H, C-H). IR (KBr,
n=cmꢁ1): 2850–2918 (CꢁH), 1721 (CꢁO), 1625 (C–Ocurc22), 1510
(CꢁC).
Cell Lines and Cytotoxic Assay Performed on Complex 2
DU145 human prostrate cancer cell line was grown in RPMI-1640
(Gibco) supplemented with 10% of fetal bovine serum (GIBCO), 5%
of L-glutamine (GIBCO) and antibiotics, under standard conditions
(37ꢀC temperature, 5% CO2 in a humidified atmosphere).
For cytotoxic assays, cells were plated in 96-well plates (Falcon, CA)
in 100 uL of culture medium. All species were dissolved in DMSO. For
each experiment drugs were serially diluted in cell culture medium to
the desired concentrations and an equal volume of the diluted solution
(100 uL=well) was added to the cells. DMSO was administered as con-
trol. Each treatment was performed in triplicate in three indipendent
experiments. Cells were continuously exposed to the curcuminoid
derivative 2 for 72 h. In order to determine the cytotoxic effect at the
end of drug incubation, MTS solution (3-(4,5-dimethylthiazol-2-yl)-
5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner
salt, Promega, 20 uL=well) was added to the cells. The plates were
incubated for 2 h at 37ꢀC and then the absorbance at 490 nm was
measured using Sirio-S (SEAC, Radim Group). Results are expressed
as mean ꢂ standard deviation (SD) of the percentage of viable cells
at each drug concentration compared to the untreated cells.
RESULTS AND DISCUSSION
Synthesis
The cyclopalladating ligand HL has been obtained through a two
step reaction: 2-phenyl-4-quinoline carboxylic acid reacts with
thionyl chloride to give rise to the corresponding acid chloride whose
esterification with cholesterol, in toluene, affords HL in 85% yield.

20
D. Pucci et al.
The synthetic pathway used to obtain the [(L)Pd(O,O)] complexes 1–3
is illustrated in Scheme 1.
In order to reach the target mononuclear cyclopalladated deriva-
tives we treated HL with palladium(II) acetato, in glacial acetic acid
solution, forming the pure acetato-bridged dimeric product,
[(L)Pd(l-OAc)]2, which was obtained in a 90% yield. The IR spec-
trum of [(L)Pd(l-OAc)]2 revealed the presence of two bands, at
1565 and 1411 cmꢁ1, assigned to the asymmetric and symmetric
stretching modes of the acetato group, confirming the formation of
the bridged acetato derivative. Moreover, a shift of the nC O band from
B
1
1717 cmꢁ1 to 1727 cmꢁ1 with respect to HL, is observed. The H NMR
spectrum of [(L)Pd(l-OAc)]2 revealed the absence of the H6 proton,
proving the formation of the bridged acetato derivative. In this spec-
trum it was also observed the presence of two isomers. According to
the literature data about of similar dimeric acetato species [6,7], we
popose that the higher signals proportion can be assigned to the trans
isomer (5:1).
The [(L)Pd(l-OAc)]2 complex is a good starting material for the
synthesis of the corresponding mononuclear ortho-palladated deriva-
tives 1-3 since the OAc anion is the appropriate leaving group to
encourage the chelation of the reacted O,O incoming ligands (Experi-
1
mental Section). All complexes have been fully characterized by H
NMR, FT-IR and elemental analysis, proving the expected
[(L)Pd(O,O)]stoichiometry.
Thermal Behaviour
Although the ligand HL is not liquid crystal, the complexation to the
palladium gave rise to the new liquid crystalline cyclopalladated com-
plexes,which all showed thermally reproducible mesomorphism,
which was evidenced by a combination of optical microscopy (POM),
differential scanning calorimetry (DSC) and powder X-ray diffraction
analysis at variable temperature (PXRD). Thermal data are summar-
ized in Table 1.
The identification of the mesophases was firstly performed by obser-
vation of the optical textures: an oily streaks texture, for [(L)Pd(l-
OAc)]2; a very fine schlieren texture for [(L)Pd(trop)], 1, and
[(L)Pd(curc)], 2. The texture of [(L)Pd(curc22)], 3, showed Maltese
crosses suggesting the existence of columnar mesomorphism. X-ray
diffraction at variable temperature were carried out to confirm the
nature of the mesophases.
The PXRD recorded at 240ꢀC of the dinuclear [(L)Pd(l-OAc)]2
derivative has revealed the presence of a chiral smectic phase through

Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin
21
TABLE 1 Thermal Properties of Complexes 1–3
Complexes
Phasesa
Transition temperatures (ꢁC)
DH=kJ molꢂ1
[(L)Pd(m-OAc)]2
[(L)Pd(trop)] 1
[(L)Pd(curc)] 2
[(L)Pd(curc22)] 3
C-Smcꢃ
Smcꢃ-I
C-Ch
195.6
225.5
135a
270a
140
220.1
53
65.2
200b
24.93
6.32
Ch-I
C-Colrect
Colrect-Idec
C-C0
C0-Colhex
Colhex-I
3.67
5.61
23.88
aCr: Crystal; Ch: Cholestric; Col: Columnar; I: Isotropic liquid
boptical data
the presence of a quite broad peak in the small angle region centred at
˚
49.5 A (Fig. 1a). The variation in the shape of the molecule, with the
introduction of the tropolone ligand causes the loss of the lamellar
order and in the case of [(L)Pd(trop)], 1, a more disordered molecular
arrangement is found. The PXRD in this case is characterized by a
broad peak at 2h ꢀ 20 deg, which is typical of a cholesteric structure
(Fig. 1b) [8].
Replacement of the tropolonate unit by the curcuminoid co-ligands
allows a peculiar combination of two different molecular architectures.
The rather rod-like pheylquinoline unit with an half-disc-shaped dike-
tonate moiety gives rise to an unusual molecular shape which deeply
influences the mesophase type. Indeed a discotic mesomorphism is
found for both curcuminoid derivatives 2 and 3.
FIGURE 1 X ray diffraction patterns of nonaligned samples of the (a) smectic
chiral phase of [(L)Pd(l-OAc)]2 and (b) cholesteric phase of 1. (See COLOR
PLATE I)

22
D. Pucci et al.
FIGURE 2 X ray diffraction pattern of a non aligned sample of 2, recorded at
180ꢀC on cooling.
The XRD pattern of 2 recorded at 180ꢀC on cooling revealed a
rectangular columnar mesophase, characterized by two sharp funda-
mental peaks in the low angle region (Fig. 2). The strong low angle
peaks are indexed as (10) and (01), leading to the indexation of the
˚
peaks in the middle angle region [calculated d (A) values for (21),
21.5, (02), 18.8, (23), 11.3, (43), 9.1] and to the calculated lattice para-
˚
˚
meters a ¼ 52.3 A and b ¼ 37.6 A.
By adding two alphatic chains to the curcumin, a transition from
rectangular to hexagonal columnar symmetry organization is found.
The XRD pattern of complex 3 is typical of a two-dimensional hexag-
onal lattice with a cell parameter a of 44.7A. In the wide angle region
a broad halo centred at 4.6 A and corresponding to the liquid-like
˚
˚
correlations between side chains, is observed.

Liquid Crystalline Cholesterol-Based Ortho-Palladated Curcumin
23
FIGURE 3 Cytotoxic activity of [(L)Pd(curc)], 2, towards DU145 and
LNCaP human prostate cancer cells.
We have investigated the cytotoxic effect of the more soluble mono-
nuclear complex, [(L)Pd(curc)] 2, against the androgen-unsensitive
(DU145) cell line, previously tested on analogous curcumin derivatives
[4], and also against an androgen-sensitive (LNCaP) human prostate
cancer cell line in order to study the influence of the cholesteryl frag-
ment on the overall framework. Cell viability was assessed after 72
hours of continuous exposure to compound 2, using a colorimetric
assay (MTS). The cytotoxic activity of curc was assessed under ident-
ical conditions and used as reference for the activity of the correspond-
ing complex.
Complex [(L)Pd(curc)], 2, induces of about 55% of cell growth
inhibition in both cell lines, at 50 mM dose, suggesting that the combi-
nation of two different molecular sub-units around a metal centre
enhances the cytotoxicity compared to curcumin and confirms the
useful approach in the synthesis of heteroleptic systems (Fig. 3).
CONCLUSIONS
The 2-phenylquinoline ligand has been functionalised with a chiral
terminal substituent, the cholesteryl ester unit, and cyclopalladated
producing a new dinuclear bridged acetato derivative in high yields.
The corresponding heteroligand mononuclear complexes [LPd(O,O)]
have been synthesizedby conjugating the cyclopalladated fragment
with O,O chelating bioactive ligands such as tropolone and cucuminoid
b-diketones. Despite of the ligand shows no mesomorphism, the

24
D. Pucci et al.
coordination to the palladium(II) has led to metallomesogenic species
for which a transition from calamitic to columnar organisation of the
molecules is observed. This transition strongly depends on the overall
molecular shape as the geometrical features of the rather calamitic
dinuclear roof-shaped acetato-bridged complex and of the mono-
nuclear tropolonate derivative lead to a more or less parallel organiza-
tion of the molecules which is favorable for disordered calamitic chiral
mesophases. The replacement of the tropolonate unit with the curcu-
minoid co-ligands leads to the calamitic=discotic cross-over point due
to the peculiar combination of two different molecular architectures:
the rather rod-like pheylquinoline unit and an half-disc-shaped diketo-
nate moiety. The resulting unusual molecular shape of the curcumin
derivatives deeply influences the molecular organization within the
mesophase, inducing the formation of columnar mesomorphism in
the case of [LPd(curc)], 2, complex. A transition from rectangular
to hexagonal columnar symmetry organization in [LPd(curc22)], 3
is due to the introduction of long flexible substituents into the curcu-
min fragment.
A promising biological activity based on the preliminary in vitro
anticancer screening against two human prostatic cancer cell lines
has been found for [(L)Pd(curc)], 2. These results prompt us to think
that, through the careful choice of the molecular building blocks, cyclo-
palladated mesogens can produce, more than purely organic species:
i) molecular shapes easily modulated; ii) multifunctional biomaterials
bearing at the same time the active principal and the delivery com-
ponent, becoming innovative tool in establishing new and effective
anticancer therapies.
Finally, it is noteworthy that the properties exhibited by the
present complexes suggest that metallomesogens can be conveniently
considered for applications requiring bioactive molecules.
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