Congested cyclometalated platinum(II) ditopic frameworks and their phosphorescent responses to S-containing amino acids

Article abstract of DOI:10.1021/om1007488

New phosphorescent platinum(II) molecular hosts featuring a tridentate N,C,N-coordinating ligand, a conformationally rigid organic linker, and a binding group have been prepared. The complexes have been fully characterized by various spectroscopic techniques, and the X-ray crystal structure of one derivative has been determined. Their photophysical properties have been studied, and intense green metal-perturbed ³IL emission is observed in solution at room temperature. The luminescent responses of these Pt(II) hosts to amino acids have been investigated: emission quenching and UV-vis absorption changes in polar/aqueous media are detected for terminal thiols only, and unusual preferential binding is apparent for cysteine over homocysteine. The nature of the host-guest interactions has been examined by quantitative and comparative binding studies, mass spectrometry, and DFT calculations, which indicate that these observations may be ascribed to the presence of rigidly positioned ditopic binding sites.

Full text of DOI:10.1021/om1007488

Organometallics 2010, 29, 6377–6383 6377
DOI: 10.1021/om1007488
Congested Cyclometalated Platinum(II) Ditopic Frameworks and Their
Phosphorescent Responses to S-Containing Amino Acids
Wah-Leung Tong, Michael C. W. Chan,* and Shek-Man Yiu
Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon,
Hong Kong, People’s Republic of China
Received July 30, 2010
New phosphorescent platinum(II) molecular hosts featuring a tridentate N,C,N-coordinating
ligand, a conformationally rigid organic linker, and a binding group have been prepared. The
complexes have been fully characterized by various spectroscopic techniques, and the X-ray crystal
structure of one derivative has been determined. Their photophysical properties have been studied,
3
and intense green metal-perturbed IL emission is observed in solution at room temperature. The
luminescent responses of these Pt(II) hosts to amino acids have been investigated: emission
quenching and UV-vis absorption changes in polar/aqueous media are detected for terminal thiols
only, and unusual preferential binding is apparent for cysteine over homocysteine. The nature of the
host-guest interactions has been examined by quantitative and comparative binding studies, mass
spectrometry, and DFT calculations, which indicate that these observations may be ascribed to the
presence of rigidly positioned ditopic binding sites.
Introduction
molecular conformations, as well as allow the reporting of
molecular-level perturbations and events.4
Interest in the development of luminescent and colori-
metric sensors and probes continues unabated.1 Design
strategies evolved from molecular phenomena, such as rigi-
dification and restricted rotation and conformation, have
been explored for fluorescent sensing applications.2 While
the focus on organic hosts has been more acute, it is evident
that transition metal-based systems can engender advan-
tages such as tunable, well-defined coordination geometries
and visible light signaling, as well as alternative binding
interactions and pathways. Our current studies are directed
toward the modular3 synthesis of crowded molecular hosts
and frameworks featuring environmentally sensitive platinum-
(II) luminophores, which have been conceived to afford unusual
photophysical characteristics and the possibility of controlling
Here, we describe the synthesis and photophysical proper-
ties of phosphorescent host complexes containing the cyclo-
metalated [N,C,N-Pt(II)] [N,C,N = 2,6-di(20-pyridyl)(σ-
aryl)] moiety and a potential binding site, which are rigidly
linked by a xanthene moiety to yield shape-persistent cavities
that only permit axial rotation of the respective components.
Square-planar polypyridyl5 and cyclometalated6,7 Pt(II)
complexes and multinuclear assemblies have been exten-
sively studied over the past three decades, owing to their
tendency to undergo interplanar stacking and metal-metal
interactions and for their diverse excited-state properties. In
particular, their open geometry facilitates the observation of
(5) (a) Miskowski, V. M.; Houlding, V. H. Inorg. Chem. 1981, 30,
4446. (b) Bailey, J. A.; Hill, M. G.; Marsh, R. E.; Miskowski, V. M.; Schaefer,
W. P.; Gray, H. B. Inorg. Chem. 1995, 34, 4591. (c) Cummings, S. D.;
Eisenberg, R. J. Am. Chem. Soc. 1996, 118, 1949. (d) Arena, G.; Calogero,
G.; Campagna, S.; Monsu Scolaro, L.; Ricevuto, V.; Romeo, R. Inorg. Chem.
1998, 37, 2763. (e) B€uchner, R.; Cunningham, C. T.; Field, J. S.; Haines, R. J.;
McMillin, D. R.; Summerton, G. C. J. Chem. Soc., Dalton Trans. 1999, 711.
(f) Kato, M.; Omura, A.; Toshikawa, A.; Kishi, S.; Sugimoto, Y. Angew.
Chem., Int. Ed. 2002, 41, 3183. (g) Wadas, T. J.; Wang, Q.-M.; Kim, Y.-J.;
Flaschenreim, C.; Blanton, T. N.; Eisenberg, R. J. Am. Chem. Soc. 2004,
126, 16841.
(6) (a) Lai, S.-W.; Chan, M. C. W.; Cheung, T.-C.; Peng, S.-M.; Che,
C.-M. Inorg. Chem. 1999, 38, 4046. (b) Lai, S.-W.; Chan, M. C. W.; Cheung,
K.-K.; Che, C.-M. Organometallics 1999, 18, 3327. (c) Lu, W.; Chan,
M. C. W.; Cheung, K.-K.; Che, C.-M. Organometallics 2001, 20, 2477. (d)
Lu, W.; Chan, M. C. W.; Zhu, N.; Che, C.-M.; Li, C.; Hui, Z. J. Am. Chem.
Soc. 2004, 126, 7639.
(7) (a) Yersin, H.; Donges, D.; Humbs, W.; Strasser, J.; Sitters, R.;
Glasbeek, M. Inorg. Chem. 2002, 41, 4915. (b) Lai, S.-W.; Lam, H.-W.; Lu,
W.; Cheung, K.-K.; Che, C.-M. Organometallics 2002, 21, 226. (c) Kui,
S. C. F.; Sham, I. H. T.; Cheung, C. C. C.; Ma, C.-W.; Yan, B.; Zhu, N.; Che,
C.-M.; Fu, W.-F. Chem.;Eur. J. 2007, 13, 417. (d) Rao, Y.-L.; Wang, S.
Inorg. Chem. 2009, 48, 7698. (e) Hudson, Z. M.; Zhao, S.-B.; Wang, R.-Y.;
Wang, S. Chem.;Eur. J. 2009, 15, 6131.
*To whom correspondence should be addressed. E-mail: mcwchan@
cityu.edu.hk.
(1) (a) de Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem.
ꢀ
ꢀ
Rev. 1997, 97, 1515. (b) Martínez-Manez, R.; Sancenon, F. Chem. Rev.
2003, 103, 4419.
(2) (a) McFarland, S. A.; Finney, N. S. J. Am. Chem. Soc. 2001, 123,
1260. (b) Mizuno, T.; Wei, W.-H.; Eller, L. R.; Sessler, J. L. J. Am. Chem.
Soc. 2002, 124, 1134. (c) McFarland, S. A.; Finney, N. S. J. Am. Chem. Soc.
2002, 124, 1178. (d) Goshe, A. J.; Steele, I. M.; Bosnich, B. J. Am. Chem.
Soc. 2003, 125, 444. (e) Wolf, C.; Mei, X. J. Am. Chem. Soc. 2003, 125,
10651. (f) Barboiu, M.; Prodi, L.; Montalti, M.; Zaccheroni, N.; Kyritsakas,
N.; Lehn, J.-M. Chem.;Eur. J. 2004, 10, 2953. (g) Nguyen, T.-Q.; Martel,
R.; Avouris, P.; Bushey, M. L.; Brus, L.; Nuckolls, C. J. Am. Chem. Soc.
2004, 126, 5234. (h) Mello, J. V.; Finney, N. S. J. Am. Chem. Soc. 2005, 127,
10124. (i) Chebny, V. J.; Rathore, R. J. Am. Chem. Soc. 2007, 129, 8458. (j)
Rurack, K.; Resch-Genger, U. Chem. Soc. Rev. 2002, 31, 116.
(3) Tong, W. L.; Chan, M. C. W.; Zhu, N.; Leung, S. K. Dalton Trans.
2009, 4741.
(4) (a) Guo, Z.; Tong, W. L.; Chan, M. C. W. Chem. Commun. 2009,
6189. (b) Guo, Z.; Chan, M. C. W. Chem.;Eur. J. 2009, 15, 12585.
r
2010 American Chemical Society
Published on Web 11/04/2010
pubs.acs.org/Organometallics

6378 Organometallics, Vol. 29, No. 23, 2010
Scheme 1. Synthesis of Complexes 1 and 2
Tong et al.
low-energy deep red fluid emissions (ascribed to metal-
metal-to-ligand charge transfer, MMLCT [dσ*fπ*] tran-
sitions), which are highly responsive to changes in the
immediate microenvironment.8 The highly emissive [N,C,
N-Pt(II)] luminophore, which was developed by Williams
and has attracted attention in material applications,9 was
chosen for this work because it is well established that the
ancillary Cl ligand in tridentate polypyridyl-Pt(II) complexes
may be labile and can undergo displacement reactions with
S- and N-donors,10 and this is particularly true for [Pt(N,C,
N)Cl] derivatives due to the strong trans effect of the σ-aryl
donor.11 We therefore proposed to exploit this lability, since
such substitution reactions should be accompanied by
photophysical perturbations. Hence, ditopic hosts featuring
one binding moiety plus an accessible and reactive Pt(II)
module (positioned directly in the cavity to augment
sensitivity) have been targeted, while the associated rigidity
may confer selectivity upon substrate binding.
(Hcy). While the sensing media used are not biocompatible,
these observations demonstrate the potential viability of the
present design approach using crowded ditopic phosphor-
escent hosts. Reports of binuclear Pt(II) complexes sup-
ported by a xanthene backbone have appeared in the
literature.4b,9d,12
Results and Discussion
Synthesis and Characterization. The conformationally ri-
gid complexes 1 and 2 (Scheme 1) are prepared from the
substituted 4,5-dibromoxanthene precursor by Pd-catalyzed
coupling reactions at elevated temperatures to give the
corresponding ligands, followed by treatment with K2PtCl4.
The benzoic acid group is incorporated as a potential binding
unit (with ester as control), and the xanthene fragment acts as
a robust and readily functionalizable backbone that links the
luminophore and binding sites. The tert-butyl groups afford
good solubility in nonpolar organic solvents such as CH2Cl2
and CH3CN by impeding π-stacking aggregation processes.
However, like the cationic terpyridine analogue,3 complex 1
displays limited aqueous solubility.
In this study, although the phosphorescent Pt(II) frame-
works display limited aqueous solubility, interesting selec-
tivity is observed in polar/aqueous media for aminothiols
over standard amino acids, and preferential binding is
unusually detected for cysteine (Cys) over homocysteine
1
Complexes 1 and 2 have been fully characterized by H
and 13C NMR spectroscopy and ESI-MS, the latter showing
a peak cluster that corresponds closely to the respective
calculated isotopic pattern (Supporting Information). The
molecular structure of 2 has been determined by X-ray
crystallography (Figure 1).13 The Pt center resides in a
distorted square-planar geometry, and the Pt-C(aryl) bond
(8) Sensing applications: (a) Liu, H.-Q.; Peng, S.-M.; Che, C.-M. J.
Chem. Soc., Chem. Commun. 1995, 509. (b) Wong, K.-H.; Chan, M. C. W.;
Che, C.-M. Chem.;Eur. J. 1999, 5, 2845. (c) Yu, C.; Chan, K. H.-Y.; Wong,
K. M.-C.; Yam, V. W.-W. Chem.;Eur. J. 2008, 14, 4577. (d) Wu, P.; Wong,
E. L.-M.; Ma, D.-L.; Tong, G. S.-M.; Ng, K.-M.; Che, C.-M. Chem.;Eur. J.
2009, 15, 3652. (e) Ma, D.-L.; Che, C.-M.; Yan, S.-C. J. Am. Chem. Soc.
2009, 131, 1835.
(9) (a) Williams, J. A. G.; Beeby, A.; Davies, E. S.; Weinstein, J. A.;
Wilson, C. Inorg. Chem. 2003, 42, 8609. (b) Farley, S. J.; Rochester, D. L.;
Thompson, A. L.; Howard, J. A. K.; Williams, J. A. G. Inorg. Chem. 2005,
44, 9690. (c) Cocchi, M.; Virgili, D.; Fattori, V.; Rochester, D. L.; Williams,
J. A. G. Adv. Funct. Mater. 2007, 17, 285. (d) Develay, S.; Williams, J. A. G.
(12) (a) Okamura, R.; Wada, T.; Aikawa, K.; Nagata, T.; Tanaka, K.
Inorg. Chem. 2004, 43, 7210. (b) Panunzi, A.; Giordano, F.; Orabona, I.;
Ruffo, F. Inorg. Chim. Acta 2005, 358, 1217. (c) Hijazi, A.; Walther, M. E.;
Besnard, C.; Wenger, O. S. Polyhedron 2010, 29, 857.
˚
(13) Crystal data for 2 (λ=0.71073 A): C47H45N2O3ClPt, fw=916.40,
˚ ˚ ˚
monoclinic, P21/c, a=19.017(5) A, b=18.540(4) A, c=11.446(5) A, β=
3 3
ꢀ
Dalton Trans. 2008, 4562. (e) Cardenas, D. J.; Echavarren, A. M.; Ramírez
˚
de Arellano, M. C. Organometallics 1999, 18, 3337.
(10) (a) Eryazici, I.; Moorefield, C. N.; Newkome, G. R. Chem. Rev.
2008, 108, 1834. (b) Cummings, S. D. Coord. Chem. Rev. 2009, 253, 1495.
(11) Hofmann, A.; Dahlenburg, L.; van Eldik, R. Inorg. Chem. 2003,
42, 6528.
97.232(3)°, crystal size 0.2 ꢀ 0.2 ꢀ 0.2 mm , V=4003.6(2) A , Z=4, Dc=
1.520 g cm-3, μ(Mo KR)=3.615 mm-1, F(000)=1840, T=293(2) K,
2θmax=50.0°, 7032 indep reflns (Rint=0.0408), 496 variable parameters,
R1=0.0263 [I >2σ(I )], w-R32=0.0491, GOF(F2)=0.932, largest diff peak/
˚
hole=0.637/-0.554 e A
.

Article
Organometallics, Vol. 29, No. 23, 2010 6379
Figure 1. Perspective view of 2 (50% probability ellipsoids; hydrogen atoms omitted for clarity).
1
charge transfer character involving Pt(II) (i.e., MLCT), in
accordance with previous reports for analogous aryl-sub-
stituted [Pt(N,C,N)Cl] complexes.9 The highly structured
green emission (λmax 504 nm; vibronic progression ≈ 1080
cm-1) observed for both 1 and 2 at 298 K in CH3CN is
attributed to a Pt-perturbed 3(π-π*) excited state, and high
quantum yields (Φ ≈ 60% in degassed CH3CN) are ob-
n
tained. The shift for the emission maxima in 77 K BuCN
glass is minimal, consistent with the predominantly ligand-
centered nature of the excited state.
In contrast to previous observations for cationic terpyr-
idine-Pt congeners3 and [N,C,N-Pt] derivatives,9b excimeric
emission was not observed for 1 and 2 for concentrations up
n
to 10-3 M in 77 K BuCN glass or DMF/H2O mixtures at
298 K. This is presumably due to the presence of the tert-
butyl groups and is beneficial for sensing studies, since host
aggregation and related complications should be circum-
vented. Minor variations for the solid-state emission maxima
between 1 and 2 (Supporting Information) are attributed to
different crystal-packing effects (strong hydrogen-bonding
interactions are possible only in 1). In general, the close
resemblance between the absorption and emission spectra of
1 and 2 signifies that the change from benzoic acid to ester
results in minimal differences in the charge-transfer transi-
tions and excited states of these complexes, which originate
from the [N,C,N-Pt(II)] moiety.
Luminescent Response of Complex 1 to Amino Acids. In
order to investigate the nature of the proposed ditopic sites
and the possibility of deriving selectivity for host systems
such as 1, binding studies with standard amino acids have
been performed by spectrofluorometric titrations in aerated
1:1 CH3CN/Tris buffer (pH 7.2) with 5% DMF (Figure 3).14
The ionization of the acid group in complex 1 was probed by
Figure 2. UV-vis absorption (black) and fluid emission (red;
λex 408 nm) spectra at 298 K (10-5 M in CH3CN) and 77 K
emission spectrum (blue; 10-3 M in nBuCN; λex 408 nm) of 1.
is noticeably shorter than the Pt-N(py) bonds [Pt(1)-C(1)
9a,b
˚
1.897(3), Pt(1)-N(1) 2.046(3), Pt(1)-N(2) 2.045(3) A].
The xanthene group is slightly puckered as expected, and
dihedral angles of 49° and 47° with the [N,C,N] and benzoate
rings, respectively, are observed. A dihedral angle of 9.7°
between the rigid [N,C,N] and benzoate fragments is incon-
sistent with the presence of π-π interactions, even though
˚
interplanar separations down to 3.53 A are apparent, and
crystal packing effects may therefore be more dominant in
determining the molecular conformation in 2.
Photophysical Properties. The UV-vis absorption and
fluid emission data for complexes 1 (Figure 2) and 2 are very
similar (Table 1). Namely, intense absorption bands at
<λmax 330 nm (ε>1 ꢀ 104 dm3 mol-1 cm-1) are assigned
1
to (π-π*) transitions, and moderately strong absorption
(14) Tris buffer composition: tris(hydroxymethyl)aminomethane
(0.1 M) and KCl (0.1 M) at pH 7.2. Precipitation was not observed
during any of the titrations described.
bands at λmax 360-410 nm (ε ≈ 4000-5000 dm3 mol-1 cm-1
)
are attributed to spin-allowed transitions with significant

6380 Organometallics, Vol. 29, No. 23, 2010
Tong et al.
Table 1. Photophysical Dataa
298 K fluid
emissionb λmax (τ; Φ)
77 K glass
emissionc λmax (τ)
complex
UV-vis λmax (ε ꢀ 103)b
260 (50.3), 335 (9.62),
1
504 (max), 533 (5.0; 0.63)
497 (max), 531, 570 (8.1)
360 (4.48), 381 (5.31), 406 (4.62)
260 (51.3), 335 (9.10),
361 (4.16), 382 (5.49), 409 (5.09)
2
504 (max), 533 (5.9; 0.62)
499 (max), 532, 572 (8.8)
a λ in nm; ε in dm3 mol-1 cm-1; λex 408 nm; lifetimes (τ) in μs. b In degassed CH3CN (10-5 M). c In nBuCN (10-3 M).
Figure 3. Binding isotherms for 1 (5.0 ꢀ 10-5 M) with amino acids in aerated 1:1 CH3CN/Tris buffer (pH 7.2) with 5% DMF.
an acid-base titration experiment,15 which indicated that
the carboxylate moiety exists at neutral pH. Apparent pKa
values ranging from 3.2 to 6.8 in organic/aqueous media
have been reported for related (oligo)pyridyl-Pt(II) carbox-
ylate derivatives.8d,16 Saliently, substantial emission quench-
ing and red-shifted UV-vis absorption bands for 1 are
detected with cysteine only (see below for quantitative
experiments),17 which is tentatively ascribed to interaction/
reaction with the -SH group (see Figure 4 and discussion).
In this regard, the lack of response for methionine is con-
sistent with the hindered lone pair and lower nucleophilicity
for the -SMe unit. Competition experiments with standard
amino acids have been conducted, indicating selectivity for
cysteine (Supporting Information).
ESI mass spectrometry was used to probe the nature of the
binding interaction (or reaction) between 1 and Cys. The
dominant signal in the ESI mass spectrum (þve mode) of the
reaction mixture containing 1 and excess cysteine using zero
declustering potential (Figure 4) is a cluster at m/z = 1009.5,
which displays excellent agreement with the calculated iso-
topic pattern for the [1 - Cl þ Cys þ Na]þ species. This
provides evidence to support the expected chloride displace-
ment and formation of the Pt-S(Cys) bond. At a decluster-
ing potential of 40 V, the cluster at m/z = 1009.5 persists, but
the [1 - Cl]þ species at m/z = 866.5 becomes more prominent
(Supporting Information), implying that the Cl ligand is indeed
labile and readily displaced under these conditions.
The facile reaction of thiols with Pt(II)-Cl bonds is well
known, and literature reports concerning the characteriza-
tion of Pt-S(cysteine)18 and Pt-S(glutathione)19 species and
the binding of [Pt(N,C,N)Cl] to intracellular thiols20 have
appeared. In addition, several classes of oligopyridyl-Pt
complexes ligated by amino acids have been described.10,21
Following the results from ESI-MS, DFT calculations have
been performed to optimize the structure of 1 (ionized; Cl-
displaced) with Cys- (Supporting Information). The energy-
minimized calculated (Gaussian) structure, which was con-
firmed to be a minimum from vibrational frequency calcula-
tions, represents a plausible binding mode in which the Cys-
moiety chelates to the ditopic host through a Pt-S bond plus
a charge-assisted hydrogen bond from the ammonium group
to the CO2- moiety (N-Hþ O 1.546 A). Nevertheless, we
˚
3 3 3
note that this gas-phase calculated structure may not repre-
sent an accurate model of the binding between 1 and Cys in
the organic/aqueous media described, where solvent effects
and competing interactions exist.
Comparative Responses of Complexes 1 and 2 to Thiols:
Preferential Binding to Cys over Hcy and Insight into Nature of
Binding. Quantitative spectrofluorometric titrations have been
ꢁ ꢀ
(18) Bugarcic, Z. D.; Heinemann, F. W.; van Eldik, R. Dalton Trans.
2004, 279.
(19) Juranic, N.; Likic, V.; Kostic, N. M.; Macura, S. Inorg. Chem.
1995, 34, 938.
ꢀ
ꢀ
ꢀ
(15) The pH change upon addition of 0.04 M NaOH(aq) to a 20 mL
stock solution of 1 (50 μM) in a mixture of 10 mM HCl and 100 mM
KCl(aq)/CH3CN (1:1 v/v) was monitored. The resultant pH change in
the buffer region was small, and the apparent pKa was estimated to be
∼5.5.
(20) Botchway, S. W.; Charnley, M.; Haycock, J. W.; Parker, A. W.;
Rochester, D. L.; Weinstein, J. A.; Williams, J. A. G. Proc. Natl. Acad.
Sci. U. S. A. 2008, 105, 16071.
(21) (a) Jin, V. X.; Ranford, J. D. Inorg. Chim. Acta 2000, 304, 38. (b)
Yajima, T.; Maccarrone, G.; Takani, M.; Contino, A.; Arena, G.; Takamido,
R.; Hanaki, M.; Funahashi, Y.; Odani, A.; Yamauchi, O. Chem.;Eur. J.
2003, 9, 3341. (c) Siu, P. K.-M.; Ma, D.-L.; Che, C.-M. Chem. Commun.
2005, 1025.
(16) Crisp, M. G.; Tiekink, E. R. T.; Rendina, L. M. Inorg. Chem.
2003, 42, 1057.
(17) The buffer concentration is an important consideration, since
partial enhancements (I/I0 up to 1.2) for aspartic and glutamic acids are
observed when very dilute buffer solutions (e.g., 0.005 M) are used.

Article
Organometallics, Vol. 29, No. 23, 2010 6381
Figure 5. Quantitative emission (λex 424 nm) and UV-vis (inset)
titrations for 1 (5.0 ꢀ 10-5 M) upon addition of cysteine (stock:
2.0 ꢀ 10-2 M) in aerated 8:2 DMF/Tris buffer (pH 7.2).
Figure 4. ESI mass spectra (þve mode) of 1 (10-4 M) and
cysteine (10 equiv.) in 8:2 DMF/Tris buffer (0.005 M; NaCl,
0.05 M; pH 7.2) using zero declustering potential: (bottom) full
spectrum; (middle) [1 - Cl þ Cys þ Na]þ species at m/z =
1009.5; (top) calculated isotopic distribution.
performed to study the response of 1 to Cys and the homo-
logous relative homocysteine (Hcy), while the medium was
changed to aerated 8:2 DMF/Tris buffer (pH 7.2)14 to enable
comparisons with the nonionizable complex 2. The UV-vis
spectral changes for 1 with Cys feature a bathochromic shift
for the lowest-energy MLCT absorption and reveal a well-
defined isosbestic point at 424 nm, which was subsequently used
as the emission λex (Figure 5). The observed red shift for the
MLCT absorption band of 1 upon treatment with Cys may be
tentatively ascribed to the nature of the resultant Pt-S(Cys)
species and the electron-rich thiolate donor, which would reduce
the electrophilicity of the Pt center and stabilize the MLCT
transition.
In the emission titrations, incremental quenching is de-
tected upon gradual addition of Cys. Concomitantly, the
aerated emission lifetime (τ504 = 0.4 μs) remains constant,
which indicates static quenching and presumably rules out
other plausible quenching pathways such as intermolecular
electron transfer. To rationalize the observed quenching, we
suggest that the presumed substitution of chloride for the
thiolate fragment would confer increased flexibility and
Figure 6. Binding isotherms for 1(black) and2(red) (5.0ꢀ 10-5 M)
with thiol substrates in aerated 8:2 DMF/Tris buffer (pH 7.2).
facilitate nonradiative decay pathways, while the attachment
of additional polar/charged moieties to the luminophore can
enhance solvent quenching processes.22 Optimal curve fitting
for 1:1 binding was performed for the emission spectral
changes, and the log K was determined to be 4.90 ( 0.01
(Supporting Information). Emission titrations for 2, and
with Hcy and the nonbiological 1-octanethiol, were also
performed to gain insight into the binding interaction and
mechanism, and the revealing results are summarized in
Figure 6 and Table 2.
First, the almost identical binding isotherms and log K
values for 1 and 2 with 1-octanethiol are strongly suggestive
of negligible involvement by the carboxylate/ester moiety
n
and a simple substitution of Cl- by the C8H17S- nucleo-
phile. Second, both 1 and 2 bind more strongly to Hcy than
1-octanethiol. The slightly higher log K for 1 (Supporting
Information) may indicate that, although the ester unit in 2
(22) The observed emission quenching and red-shifted MLCT ab-
sorption are also consistent with the introduction of greater ligand-to-
ligand charge transfer (LLCT) character. Similar changes have been
detected for related Pt(II) systems upon incorporation of electron-rich
substituents: (a) Wong, K. M. C.; Tang, W. S.; Lu, X. X.; Zhu, N.; Yam,
V. W. W. Inorg. Chem. 2005, 44, 1492. (b) Han, X.; Wu, L.-Z.; Si, G.; Pan,
J.; Yang, Q.-Z.; Zhang, L.-P.; Tung, C.-H. Chem.;Eur. J. 2007, 13, 1231.
can engage in ion-dipole H-bonding (MeOCdO Hþ-N)
3 3 3
with Hcy, the corresponding Coulombic attraction between
-
1 and Hcy (CO2
Hþ-N) should be more favorable.
Third, the binding to Cys is clearly the strongest for both 1
3 3 3

6382 Organometallics, Vol. 29, No. 23, 2010
Tong et al.
Table 2. Calculated log K for 1 and 2 with Thiol Substrates (1:1
binding) in Aerated 8:2 DMF/Tris Buffer (pH 7.2)
human diseases such as neurotoxicity, growth problems,
and cardiovascular and Alzheimer’s diseases.27
thiol substrate
1
2
Summary
cysteine
homocysteine
1-octanethiol
log K = 4.90 ( 0.01
log K = 3.65 ( 0.06
log K = 2.93 ( 0.03
log K = 3.80 ( 0.07
log K = 3.42 ( 0.11
log K = 2.94 ( 0.03
Compared with our recent report employing terpyridine-
Pt(II) moieties, the present work describes a host system
containing the highly emissive [N,C,N-Pt(II)] luminophore.
The new complexes have been fully characterized, and their
photophysical properties and potential to act as selective
phosphorescent probes have been investigated. By utilizing
the known propensity for terminal thiols to coordinate to
Pt(II), we have integrated the [N,C,N-Pt(II)] and carboxylate
binding sites to afford a crowded molecular framework that
displays unusual preferential binding for Cys over Hcy, while
no binding is detected for methionine. In this regard, the
preorganized, shape-persistent binding pocket maintained by
the rigid xanthene backbone undoubtedly plays a critical role in
differentiating the thiol-containing species, and the enhanced
binding with Cys is attributed to the superior ditopic spatial
fit and greater complementarity. Insight into the nature of
the host-guest interaction has also been obtained from the
binding behavior of the ester congener. While we are not
advocating this system as a practical sensor for distinguishing
biological thiols (the sensing media are not biocompatible),
we consider that the development of this design approach,
based on congested ditopic hosts bearing responsive phos-
phorescent reporting units, is worthwhile.
and 2, and the above Coulombic argument is again invoked
to rationalize the significantly higher log K for 1, as predicted
by the DFT calculations described above.
Previously reported luminescent and colorimetric probes
for biological thiols are often nondiscriminating,23,24 or
selectivity for Hcy over Cys is obtained (due to steric
reasons).25 Indeed, sensors capable of Cys-over-Hcy selec-
tivity are rare.26 In this context, the noticeably higher log K
for the binding of 1 to Cys compared with Hcy is intriguing.
Even though the selectivity for Cys over Hcy (KCys/KHcy
=
17.8) is modest, we suggest that the binding cavity in 1
affords a superior ditopic spatial fit and enhanced comple-
mentarity for the shorter Cys. Hence, we consider the pre-
ferential binding of 1 to the more sterically hindered Cys over
Hcy to be the initial realization of the crowded ditopic
phosphorescent host concept postulated in this work. The
selective recognition of biomolecules and their structural
motifs is appealing for, inter alia, probing biological path-
ways and designing new therapeutic agents. The detection of
Cys and Hcy is important because abnormal levels of these
biological thiols are associated with a wide spectrum of
Experimental Section
(23) (a) Rusin, O.; St. Luce, N. N.; Agbaria, R. A.; Escobedo, J. O.;
Jiang, S.; Warner, I. M.; Dawan, F. B.; Lian, K.; Strongin, R. M. J. Am.
Chem. Soc. 2004, 126, 438. (b) Tanaka, F.; Mase, N.; Barbas, C. F., III.
Chem. Commun. 2004, 1762. (c) Maeda, H.; Matsuno, H.; Ushida, M.;
Katayama, K.; Saeki, K.; Itoh, N. Angew. Chem., Int. Ed. 2005, 44, 2922. (d)
Shao, N.; Jin, J. Y.; Cheung, S. M.; Yang, R. H.; Chan, W. H.; Mo, T. Angew.
Chem., Int. Ed. 2006, 45, 4944. (e) Zhang, M.; Yu, M.; Li, F.; Zhu, M.; Li,
M.; Gao, Y.; Li, L.; Liu, Z.; Zhang, J.; Zhang, D.; Yi, T.; Huang, C. J. Am.
Chem. Soc. 2007, 129, 10322. (f) Sreejith, S.; Divya, K. P.; Ajayaghosh, A.
Angew. Chem., Int. Ed. 2008, 47, 7883. (g) Bouffard, J.; Kim, Y.; Swager,
T. M.; Weissleder, R.; Hilderbrand, S. A. Org. Lett. 2008, 10, 37. (h) Lee,
J.-S.; Ulmann, P. A.; Han, M. S.; Mirkin, C. A. Nano Lett. 2008, 8, 529. (i) Lin,
W.; Yuan, L.; Cao, Z.; Feng, Y.; Long, L. Chem.;Eur. J. 2009, 15, 5096. (j)
Yao, Z.; Feng, X.; Li, C.; Shi, G. Chem. Commun. 2009, 5886. (k) Huo, F.-J.;
Sun, Y.-Q.; Su, J.; Chao, J.-B.; Zhi, H.-J.; Yin, C.-X. Org. Lett. 2009, 11, 4918.
(l) Shao, N.; Jin, J.; Wang, H.; Zheng, J.; Yang, R.; Chan, W. H.; Abliz, Z. J. Am.
Chem. Soc. 2010, 132, 725. (m) Lee, J. H.; Lim, C. S.; Tian, Y. S.; Han, J. H.;
Cho, B. R. J. Am. Chem. Soc. 2010, 132, 1216. (n) Chen, X.; Ko, S.-K.; Kim,
M. J.; Shin, I.; Yoon, J. Chem. Commun. 2010, 46, 2751. (o) Liu, J.; Bao, C.;
Zhong, X.; Zhao, C.; Zhu, L. Chem. Commun. 2010, 46, 2971.
(24) Phosphorescent examples: (a) Chow, C.-F.; Chiu, B. K.-W.;
Lam, M. H.-W.; Wong, W.-Y. J. Am. Chem. Soc. 2003, 125, 7802. (b)
Huang, K.; Yang, H.; Zhou, Z.; Chen, H.; Li, F.; Yi, T.; Huang, C. Inorg.
Chim. Acta 2009, 362, 2577.
(25) For example: (a) Wang, W.; Escobedo, J. O.; Lawrence, C. M.;
Strongin, R. M. J. Am. Chem. Soc. 2004, 126, 3400. (b) Lee, K.-S.; Kim,
T.-K.; Lee, J. H.; Kim, H.-J.; Hong, J.-I. Chem. Commun. 2008, 6173. (c)
Shiu, H.-Y.; Chong, H.-C.; Leung, Y.-C.; Wong, M.-K.; Che, C.-M. Chem.;
Eur. J. 2010, 16, 3308. Phosphorescent: (d) Chen, H.; Zhao, Q.; Wu, Y.; Li,
F.; Yang, H.; Yi, T.; Huang, C. Inorg. Chem. 2007, 46, 11075.
(26) Colorimetric: (a) Han, M. S.; Kim, D. H. Tetrahedron 2004, 60,
11251. (b) Wang, W.; Rusin, O.; Xu, X.; Kim, K. K.; Escobedo, J. O.;
Fakayode, S. O.; Fletcher, K. A.; Lowry, M.; Schowalter, C. M.; Lawrence,
C. M.; Fronczek, F. R.; Warner, I. M.; Strongin, R. M. J. Am. Chem. Soc.
2005, 127, 15949. Fluorescent: (c) Li, H.; Fan, J.; Wang, J.; Tian, M.; Du, J.;
Sun, S.; Sun, P.; Peng, X. Chem. Commun. 2009, 5904. Circular dichroism
probe: (d) Nan, J.; Yan, X.-P. Chem.;Eur. J. 2010, 16, 423.
(27) (a) Selhub, J.; Jacques, P. F.; Bostom, A. G.; D’Agostino, R. B.;
Wilson, P. W. F.; Belanger, A. J.; O’Leary, D. H.; Wolf, P. A.; Schaefer,
E. J.; Rosenberg, I. H. N. Engl. J. Med. 1995, 332, 286. (b) Seshadri, S.;
Beiser, A.; Selhub, J.; Jacques, P. F.; Rosenberg, I. H.; D'Agostino, R. B.;
Wilson, P. W. F.; Wolf, P. A. N. Engl. J. Med. 2002, 346, 476. (c) See
citations in ref 26b.
General Considerations. All reactions were performed under a
nitrogen atmosphere, and solvents for syntheses (analytical
grade) were used without further purification. Solvents for
photophysical measurements were purified according to con-
ventional methods. 1H NMR spectra were obtained on a Bruker
DRX 400 FT-NMR spectrometer (ppm) using Me4Si as internal
standard. ESI mass spectra were measured on a Perkin-Elmer
Sciex API 150EX mass spectrometer. IR spectra were recorded
on a Perkin-Elmer 1600 series FT-IR spectrophotometer. Ele-
mental analyses were performed on an Elementar Analysensys-
teme GmbH Vario EL elemental analyzer.
Photophysical Measurements. UV-vis absorption spectra
were obtained on an Agilent 8453 diode array spectrophot-
ometer. Steady-state emission spectra were recorded on a SPEX
FluoroLog 3-TCSPC spectrophotometer equipped with a Ha-
mamatsu R928 PMT detector, and emission lifetime measure-
ments were conducted using NanoLed sources in the fast MCS
mode and checked using the TCSPC mode. Low-temperature
(77 K) emission spectra for glasses and solid-state samples were
recorded in 5 mm diameter quartz tubes, which were placed in a
liquid nitrogen Dewar equipped with quartz windows. Unless
otherwise stated, 298 K emission spectra were recorded using
aerated solutions. The emission quantum yield was measured28
by using [Ru(bpy)3](PF6)2 in degassed acetonitrile as the stan-
dard (Φr = 0.062) and calculated by Φs = Φr(Br/Bs)(ns/nr)2(Ds/
Dr), where the subscripts s and r refer to sample and reference
standard solution respectively, n is the refractive index of the
solvents, D is the integrated intensity, and Φ is the luminescence
quantum yield; sample and standard solutions for this pur-
pose were degassed with at least three freeze-pump-thaw
cycles. The quantity B is calculated by the equation B = 1 - 10-AL
,
where A is the absorbance at the excitation wavelength and L is
the optical path length. Errors for λ ((1 nm), τ ((10%), and
Φ ((10%) are estimated. For the UV-vis absorption and emission
(28) Demas, J. N.; Crosby, G. A. J. Phys. Chem. 1971, 75, 991.

Article
Organometallics, Vol. 29, No. 23, 2010 6383
titration experiments, the platinum complexes (50 μM) in CH3CN/
Tris (1:1 v/v; 5% DMF) or DMF/Tris (8:2 v/v) solution
were titrated with amino acids and other thiol-containing sub-
strates (20 mM) dissolved in Tris buffer. The emission and
UV-vis absorption spectra of the aerated solution were mea-
sured after successive additions of the substrate solution at 1 min
intervals.
by column chromatography on alumina oxide (gradient elution
from 100% hexane to 8:2 CH2Cl2/MeOH) afforded a yellow
solid (0.061 g, 51%). Recrystallization in a Et2O/MeOH mix-
ture gave small yellow crystals. Anal. Calcd for C47H45ClN2-
O3Pt (916.40): C, 61.60; H, 4.95; N, 3.06. Found: C, 61.37; H,
5.23; N, 3.17. IR (KBr, cm-1): 2960, 1700. 1H NMR (400 MHz,
CD2Cl2): δ 9.29-9.28 (m, 2H, Ha), 7.89 (t, J = 7.8 Hz, 2H, Hc),
7.52-7.51 (m, 2H, Hg,h), 7. 42 (d, J = 7.9 Hz, 2H, Hd), 7.41
(s, 2H, He), 7.41 (d, J = 7.9 Hz, 2H, Hk), 7.33-7.31 (m, 3H, Hb, f/i),
7.28 (d, J = 7.7 Hz, 2H, Hj), 7.20 (d, J = 2.2 Hz, 1H, Hf/i), 3.87
(s, 3H, OMe), 1.77 (s, 6H, Hn), 1.40 (s, 9H, Hl/m), 1.35
(s, 9H, Hl/m). 13C NMR (101 MHz, CD2Cl2): δ 167.7, 166.4,
160.9, 152.2, 146.3, 146.2, 145.6, 145.1, 142.9, 141.0, 139.4,
133.5, 130.3, 130.3, 130.0, 129.7, 129.2, 128.4, 128.3, 126.4,
126.3, 126.0, 123.6, 123.3, 122.6, 119.8, 52.5, 35.4, 34.9, 34.9,
32.9, 31.7, 31.6. ESI-MS (þve mode, MeOH): m/z 917 [M þ 1]þ.
Synthetic Procedures. Synthetic details for the ligands are
given in the Supporting Information. Complex 1: A mixture of
K2PtCl4 (0.062 g, 0.148 mmol) in water (3 mL) and the N,C,N-
xanthene-benzoic acid ligand (0.100 g, 0.148 mmol) in CH3CN/
CH2Cl2 (10 mL, 9:1) was refluxed for 72 h to give a yellow
solution. The organic phase was extracted with CH2Cl2 (50 mL)
and washed with water (3 ꢀ 50 mL). The solvent was then
removed by evaporation in vacuo, and the resultant residue was
washed with pentane, then recrystallized by vapor diffusion of
Et2O into a CH2Cl2 mixture to give a yellow solid (0.088 g,
66%). Anal. Calcd for C46H43ClN2O3Pt (902.38): C, 61.23; H,
4.80; N, 3.10. Found: C, 61.54; H, 5.19; N, 3.06. IR (KBr, cm-1):
1
3450, 2960, 1720. H NMR (400 MHz, CD2Cl2): δ 9.22-9.21
(m, 2H, Ha), 7.93-7.89 (m, 2H, Hc), 7.52-7.51 (m, 2H, Hg,h),
7.42 (d, J = 8.3 Hz, 4H, Hd,k), 7.38 (s, 2H, He), 7.36-7.34 (m,
2H, Hb), 7.32 (d, J = 2.3 Hz, 1H, Hf/i), 7.27 (d, J = 8.3 Hz, 2H,
Hj), 7.21 (d, J = 2.3 Hz, 1H, Hf/i), 2.96 (s, 1H, OH; assigned
using D2O), 1.78 (s, 6H, Hn), 1.40 (s, 9H, Hl/m), 1.36 (s, 9H, Hl/m).
13C NMR (101 MHz, CD2Cl2): δ 167.5, 167.5, 167.4, 160.0,
152.3, 146.3, 146.2, 145.5, 145.1, 143.1, 140.9, 139.5, 133.75,
130.3, 130.3, 129.9, 129.7, 128.5, 128.1, 126.2, 126.1, 125.9, 123.9,
123.3, 122.7, 119.8, 35.4, 34.9, 34.9, 32.9, 31.7, 31.7. ESI-MS (þve
mode, MeOH): m/z 903 [M þ 1]þ.
Acknowledgment. The work described in this paper
was fully supported by a grant from the Research Grants
Council of the Hong Kong Special Administrative Re-
gion, China (CityU 100405). W.-L.T. acknowledges re-
ceipt of a Postgraduate Studentship administered by City
University of Hong Kong. We are grateful to Mr. Siu-
Chung Chan and Mr. Zhengqing Guo for technical
assistance.
Supporting Information Available: CIF for 2; experimental
details and characterization data; photophysical data and spec-
tra; curve fittings for substrate binding; details of molecular
modeling. This material is available free of charge via the
Internet at http://pubs.acs.org.
Complex 2 was similarly prepared using the N,C,N-xanthene-
ester ligand. The solvent was evaporated in vacuo, and purification