Two-photon-activated ligand exchange in platinum(II) complexes

Article abstract of DOI:10.1002/anie.201206283

Two photons are better than one: A square-planar Pt^II complex with derivatized pyridine ligands was synthesized (see scheme), which undergoes two-photon-induced ligand substitution with 600-740 nm light. Linear and quadratic density functional response theory allowed identification of the electronic transitions involved. Copyright

Full text of DOI:10.1002/anie.201206283

Angewandte
Chemie
DOI: 10.1002/anie.201206283
Platinum Chemistry
Two-Photon-Activated Ligand Exchange in Platinum(II) Complexes**
Yao Zhao, Gareth M. Roberts, Simon E. Greenough, Nicola J. Farrer, Martin J. Paterson,
William H. Powell, Vasilios G. Stavros,* and Peter J. Sadler*
Two-photon absorption (TPA) was theoretically proposed in
1931;[1] (near-)simultaneous absorption of two photons
(approximately 10À16 s) by an atom or molecule can drive
a transition equivalent to the absorption of a single photon of
twice the energy,[2] ultimately activating the same photo-
physical or photochemical processes induced by one-photon
absorption (OPA).[2,3] However, TPA probabilities are typi-
cally extremely small, and the first experimental evidence of
TPA was not obtained until the 1960s, using a ruby laser.[4]
Now femtosecond (fs) laser systems, which generate very high
instantaneous photon densities, have opened up a plethora of
multiphoton applications,[5] such as fluorescence microscopy[6]
and photodynamic therapy (PDT).[7]
nyl)ethynyl]pyridine (MOPEP) since we believed it would
have potential for TPA. Reported work has shown that large
TPA cross-sections (d) are often associated with long, co-
planar p-conjugated chains with opposing terminal donor and
acceptor (D-A) moieties.[2,11] Complex 1 was synthesized as
shown in Scheme 1. The cis geometry of the product was
determined by 195Pt NMR spectroscopy (see Supporting
Information).
Herein, we report the first TPA-induced ligand substitu-
tion on a square-planar PtII complex. We compare OPA with
TPA, and we use linear and quadratic density functional
response theory to identify the electronic transitions involved
and rationalize the wavelength dependence of the TPA. There
has been broad interest in controlling the reactivity of PtII
centers because of the clinical use of PtII drugs for the
treatment of cancer. Platinum anticancer prodrugs such as
PtIV diazidodihydroxido complexes[8] and PtIV dichloridodi-
hydroxido or tetrachlorido complexes[9] are effective with
OPA using UVA, or blue light, and are thus more suitable for
surface tumors, whereas deeper tissue penetration requires
longer wavelengths (620–850 nm).[10]
Scheme 1. Synthesis of the complex cis-[PtCl2(MOPEP)2] (1).
The absorption spectra of 1 and MOPEP in acetonitrile
(MeCN) are shown in the Supporting Information, Figure S3.
MOPEP has two major absorption bands centered at l =
297 nm and 310 nm, which are both assigned to intra-
molecular charge-transfer (CT) transitions. The absorption
centered at 344 nm for 1 can be assigned to a number of
metal-to-ligand charge-transfer (MLCT) transitions; see
Supporting Information for further details. In MeCN, 1 has
no absorbance greater than 500 nm and is stable in the dark
and upon irradiation with light l > 500 nm. 1 was also stable in
MeCN when heated to 343–353 K (MeCN b.p. = 355 K). The
melting of 1 was investigated and decomposition was
observed only above 473 K.
The photodecomposition of 1 in MeCN following OPA
was studied by UV/Vis absorption spectroscopy. Upon
irradiation of 1 with UVA (l = 330–380 nm, Figure 1a) or
broadband white light (l = 400–700 nm, Figure 1b), the
intensity of the major absorption band for 1 (at 344 nm)
decreased. After irradiation with UVA for five minutes
(Figure 1a, green curve) or white light for 30 minutes (Fig-
ure 1b, magenta curve), the absorbance at 344 nm disap-
peared, indicating complete photodecomposition of 1. Con-
comitantly, two strong absorption bands at approximately
300 nm emerged in the spectra; these display the same
spectral profile as the MOPEP ligand (Figure S3). This
suggests that photodecomposition of 1 proceeds by substitu-
tion of the MOPEP ligands with solvent MeCN molecules
(Scheme 2). After only one minute of irradiation with UVA,
no recovery of 1 was observed (after 12 hours in the dark), as
determined by UV/Vis spectroscopy. Notably, the rate of
photodecomposition upon irradiation with UVA was much
faster than with the broadband white light despite the lower
power density of the UVA source. This is in agreement with
We designed the novel PtII complex, cis-[PtCl2(MOPEP)2]
(1) containing the p-conjugated ligand 4-[2-(4-methoxyphe-
[*] Dr. Y. Zhao, Dr. G. M. Roberts,[+] S. E. Greenough,[+] Dr. N. J. Farrer,
W. H. Powell, Prof. Dr. V. G. Stavros, Prof. Dr. P. J. Sadler
Department of Chemistry, University of Warwick
Coventry, CV4 7AL (UK)
E-mail: v.stavros@warwick.ac.uk
p.j.sadler@warwick.ac.uk
Dr. M. J. Paterson
Institute of Chemical Sciences, Heriot-Watt University
Edinburgh, EH14 4AS (UK)
[+] These authors contributed equally to this work.
[**] Y.Z. thanks the University of Warwick and ORSAS for PhD funding.
G.M.R. thanks the Leverhulme Trust for postdoctoral funding.
S.E.G. thanks the EPSRC for a doctoral training studentship. M.J.P.
thanks the European Research Council for funding under the
European Union’s Seventh Framework Programme (FP7/2007-
2013)/ERC Grant No. 258990. V.G.S. thanks the EPSRC for equip-
ment grants (EP/E011187 and EP/H003401), the Royal Society for
a University Research Fellowship and the University of Warwick for
an RDF Award. N.J.F. and P.J.S. thank the EPSRC (EP/G006792/1)
and the ERC (award no. 247450).
Supporting information for this article (experimental details) is
available on the WWW under http://dx.doi.org/10.1002/anie.
201206283.
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Figure 2. Wavelength dependence of pseudo-first-order rate constant
(k) for TPA induced decomposition of 1 upon irradiation with femto-
second laser pulses (&, top and right axes). For comparison, the UV/
Vis spectrum of 1 is shown with a solid line (left and bottom axes).
These measurements suggest that the reaction initiated by
TPA follows the same course as that from OPA using UVA
light.
The wavelength dependence of TPA-induced decomposi-
tion between 600 and 740 nm, was monitored by UV/Vis
spectroscopy. This TPA wavelength range correlates with the
maximum OPA absorption band for 1 in Figure 2. The photon
density per femtosecond laser pulse (photonscmÀ2 pulseÀ1)
was maintained constant across the entire wavelength range
(see Supporting Information). The pseudo-first-order photo-
decomposition rate constants (k) were calculated from the
decrease in absorbance at 344 nm at each TPA wavelength
and are plotted in Figure 2.
Several control experiments were also carried out.
Irradiation with an unfocused femtosecond laser at 700 nm
resulted in negligible TPA-induced decomposition of 1,
whereas OPA from an unfocused femtosecond laser between
300–400 nm did activate photodecomposition. These control
experiments confirm that when the photon density of red light
(600–740 nm) is sufficiently high, TPA induced decomposi-
tion of 1 can be readily initiated.
Figure 1. Photoactivation of 1 upon irradiation with a) UVA and
b) white light in MeCN at 298 K for various times followed by UV/Vis
absorption spectroscopy.
Figure S3, which suggests that only light below approximately
430 nm in the white light continuum is effectively absorbed by
1.
The photodecomposition of 1 in MeCN was also exam-
ined using 600 MHz 1H NMR spectroscopy and HPLC-
coupled MS analysis. The results of these analyses are
consistent with the UV/Vis data (see Supporting Informa-
tion). Irradiation over longer periods of time in both experi-
ments (more than five minutes by UVA and more than
30 minutes by white light) caused the major absorption bands
corresponding to free MOPEP to decay in intensity, suggest-
ing additional decomposition of the photodissociated
MOPEP ligand (see Supporting Information).
When a solution of 1 in MeCN was irradiated with focused
femtosecond laser pulses, at wavelengths of 600–740 nm,
a decrease in the intensity of the major absorption band for
1 (l = 344 nm) was observed, analogous to the OPA measure-
ments. The reaction mixture was analyzed by ESI-MS and
a signal for the MOPEP ligand (m/z = 210.1 for [M+H]+) was
observed. HPLC was also used to analyze the photoproducts
from TPA activation. Figures S6 f,g are the chromatograms of
1 in MeCN upon irradiation with a femtosecond laser at
640 nm for 15 and 45 minutes, respectively. They show that
free MOPEP ligands and a small amount of [PtCl2(MOPEP)-
(MeCN)] are produced after 15 minutes of TPA activation,
and that 1 was completely photodegraded after 45 minutes.
Figure 2 highlights that the wavelength for the maximum
observed value for k (approximately 620 nm) appears blue-
shifted (by about 70 nm) with respect to the corresponding
maximum for the OPA peak (2l ꢀ 690 nm). To further
understand this shift, linear and quadratic density functional
response theory calculations were carried out to determine
both the OPA oscillator strengths and TPA cross-sections for
the electronic transitions of 1 (Figure 3a, Table S3), using the
CAM-B3LYP functional.[12] OPA calculations were per-
formed using standard linear-response time-dependent den-
sity functional theory (TD-DFT) as implemented in Gaussian
09,[13] while the TPA cross-sections were obtained as the single
residue of the quadratic response function in the Dalton 2.0
program.[14] It is only recently that accurate
TPA data have been obtained from com-
putation owing to advances in non-linear
response theory.[2,15] Specifically, the
response theory approach obviates the
need for the explicit construction of sum-
over-states expressions. Thus, the chosen
Scheme 2. Photoinduced decomposition pathways for 1.
functional needs to be more robust than for
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ligands; see Supporting Information) lie at TPA wavelengths
around 70 nm shorter than the calculated OPA maximum, in
excellent agreement with our experimental observations. In
contrast, however, the MLCT states (which exhibit the largest
OPA oscillator strengths) possess only minor TPA cross-
sections. This also corresponds with the experimentally
observed blue-shift for the TPA maximum relative to the
OPA maximum, and further explains why the traditional
expectation that lTPA ꢀ 2lOPA[3,19] is not observed for 1.
In conclusion, we report the first TPA-induced ligand
substitution for a square-planar complex; the dissociation of
the pyridine derivative MOPEP from cis-[PtCl2(MOPEP)2].
The MOPEP ligands exhibit very efficient photolability upon
irradiation with UVA, visible, and also femtosecond laser
irradiation between 600 nm and 740 nm. The enhanced
photolabilization demonstrated here may be useful in the
design of novel photoactivatable platinum chemotherapeutic
agents in situations where deep tissue penetration is needed.
Received: August 5, 2012
Published online: October 9, 2012
Keywords: density functional calculations · ligand design ·
ligand substitution · platinum · two-photon absorption
.
Figure 3. a) Density functional response theory calculated OPA oscil-
lator strengths, f (blue, left and bottom axes) and TPA cross-sections,
d (red, top and right axes) for 1 in the gas phase (for further details
see Supporting Information). b) Schematic diagram of the dissociation
mechanism following OPA and TPA. GS=ground state; LE=localized
CT state on MOPEP ligands.
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À
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