23 research outputs found
Design and Synthesis of Tris-Heteroleptic Cyclometalated Iridium(III) Complexes Consisting of Three Different Nonsymmetric Ligands Based on Ligand-Selective Electrophilic Reactions via Interligand HOMO Hopping Phenomena
In
this article we report on the successful synthesis and isolation
of cyclometalated Ir complexes having three different nonsymmetric
ligands based on ligand-selective electrophilic reactions via interligand
HOMO (highest occupied molecular orbital) hopping phenomena. It was
hypothesized that the electrophilic substitution reactions of bis-heteroleptic
Ir complexes having 8-benzenesulfonamidoquinoline as an ancillary
ligand, <b>5a</b> and <b>7</b>, would proceed at the 5
position of the quinoline ring of these Ir complexes to afford <b>18</b> and <b>19</b>, because their HOMOs are localized
on the quinoline rings, as predicted by density functional theory
(DFT) calculations. In these products, the HOMO is transferred to
one of two ppy ligands, in which the phenyl group is <i>trans</i> to the Ir–N (1 position of quinoline) bond, and hence, the
iodination or formylation of <b>18</b> and <b>19</b> occurs
at the 5′ position of the ppy ligand to provide <b>20a</b>, <b>23</b>, and <b>24</b>. Furthermore, we carried out
the functionalization of <b>20a</b> using cross-coupling reactions
to obtain tris-heteroleptic Ir complexes containing three different
ligands in good yields with negligible diastereomer formation. Photochemical
properties, especially dual emission, and response to pH change, of
new dual-emissive tris-heteroleptic cyclometalated Ir complexes, <b>21</b>–<b>24</b>, are also reported
Synthesis and Photochemical Properties of pH Responsive Tris-Cyclometalated Iridium(III) Complexes That Contain a Pyridine Ring on the 2‑Phenylpyridine Ligand
In
our previous publication, it was reported that <i>fac</i>-IrÂ(atpy)<sub>3</sub> <b>3</b> (atpy = 2-(5′-amino-4′-tolyl)Âpyridine),
which contains three amino groups at the 5′-position of the
atpy ligands, exhibits a pH-dependent change in the color of the emitted
radiation. Aqueous solution of <b>3</b> shows a weak red emission
(at around 613 nm) under neutral or basic conditions, but the emission
color changes to green (at around 530 nm) under acidic conditions,
where the NH<sub>2</sub> group is protonated to become an electron-withdrawing
(NH<sub>3</sub>)<sup>+</sup> group. In this manuscript, we report
on the preparation of some new pH-responsive IrÂ(III) complexes; <i>fac</i>-IrÂ(4Pyppy)<sub>3</sub> <b>5</b> and <i>fac</i>-IrÂ(3Pyppy)<sub>3</sub> <b>6</b> that contain three pyridyl
groups at the 5′-position of the 2-phenylpyridine (ppy) ligand,
and IrÂ(4Pyppym)<sub>3</sub> <b>7</b> and IrÂ(3Pyppym)<sub>3</sub> <b>8</b> that contain a pyridyl group at the same position
of the 2-phenylpyrimidine (ppym) ligand. The introduction of three
pyridyl groups on iodinated IrÂ(ppy)<sub>3</sub> and IrÂ(ppym)<sub>3</sub> was achieved via Suzuki–Miyaura cross-coupling reaction assisted
by microwave irradiation. Solutions of the acid-free IrÂ(III) complexes <b>5</b>, <b>6</b>, <b>7</b>, and <b>8</b> showed
a strong green emission (at around 500 nm) in dimethylsulfoxide (DMSO).
Protonation of three pyridyl groups of <b>5</b> and <b>7</b> causes a significant red-shift in the emission wavelength (at around
600 nm) with a decrease in emission intensity. The pH-dependent emission
change of these complexes is also discussed. The generation of singlet
oxygen (<sup>1</sup>O<sub>2</sub>) by the photoirradiation of the
Ir complexes <b>5</b> and <b>6</b> was evidenced by the
decomposition of 1,3-diphenylisobenzofuran (DPBF), the oxidation of
thioanisole, and the oxidation of 2,2,5,5-tetramethyl-3-pyrroline-3-carboxamide
(TPC). The induction of necrosis-like cell death of HeLa-S3 cells
upon photoirradiation of <b>5</b> at 465 nm is also reported
<sup>11</sup>B NMR Sensing of d-Block Metal Ions in Vitro and in Cells Based on the Carbon–Boron Bond Cleavage of Phenylboronic Acid-Pendant Cyclen (Cyclen = 1,4,7,10-Tetraazacyclododecane)
Noninvasive magnetic resonance imaging (MRI) including the “chemical shift imaging (CSI)” technique based on <sup>1</sup>H NMR signals is a powerful method for the in vivo imaging of intracellular molecules and for monitoring various biological events. However, it has the drawback of low resolution because of background signals from intrinsic water protons. On the other hand, it is assumed that the <sup>11</sup>B NMR signals which can be applied to a CSI technique have certain advantages, since boron is an ultratrace element in animal cells and tissues. In this manuscript, we report on the sensing of biologically indispensable d-block metal cations such as zinc, copper, iron, cobalt, manganese, and nickel based on <sup>11</sup>B NMR signals of simple phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane), L<sup>6</sup> and L<sup>7</sup>, in aqueous solution at physiological pH. The results indicate that the carbon–boron bond of L<sup>6</sup> is cleaved upon the addition of Zn<sup>2+</sup> and the broad <sup>11</sup>B NMR signal of L<sup>6</sup> at 31 ppm is shifted upfield to 19 ppm, which corresponds to the signal of B(OH)<sub>3</sub>. <sup>1</sup>H NMR, X-ray single crystal structure analysis, and UV absorption spectra also provide support for the carbon–boron bond cleavage of ZnL<sup>6</sup>. Because the cellular uptake of L<sup>6</sup> was very small, a more cell-membrane permeable ligand containing the boronic acid ester L<sup>7</sup> was synthesized and investigated for the sensing of d-block metal ions using <sup>11</sup>B NMR. Data on <sup>11</sup>B NMR sensing of Zn<sup>2+</sup> in Jurkat T cells using L<sup>7</sup> is also presented
Design and Synthesis of Heteroleptic Cyclometalated Iridium(III) Complexes Containing Quinoline-Type Ligands that Exhibit Dual Phosphorescence
The
design and synthesis of some cyclometalated iridiumÂ(III) complexes
containing quinoline-type ligands as ancillary ligands are reported.
The emission spectra of IrÂ(III) complexes containing a quinolinolate
(<b>6</b>, <b>8</b>, <b>10</b>) moiety exhibit a
single emission peak at ca. 590 nm, resulting in a red colored emission.
However, IrÂ(III) complexes containing 8-sulfonamidoquinoline ligands
(<b>11</b>, <b>13</b>–<b>21</b>) exhibit
two different emission peaks (dual emission) at ca. 500 nm and ca.
600 nm upon excitation at 366 nm, resulting in a red-colored emission
for <b>11</b> and a pale yellow-colored emission for <b>14</b>–<b>18</b> at 298 K. Especially, a white emission was
observed for <b>19</b> at 298 and 77 K in dimethyl sulfoxide.
The mechanistic studies based on time-dependent density functional
theory calculations and time-resolved emission spectroscopy suggest
that this dual emission originates from two independent emission states
<sup>11</sup>B NMR Sensing of d-Block Metal Ions in Vitro and in Cells Based on the Carbon–Boron Bond Cleavage of Phenylboronic Acid-Pendant Cyclen (Cyclen = 1,4,7,10-Tetraazacyclododecane)
Noninvasive magnetic resonance imaging (MRI) including the “chemical shift imaging (CSI)” technique based on <sup>1</sup>H NMR signals is a powerful method for the in vivo imaging of intracellular molecules and for monitoring various biological events. However, it has the drawback of low resolution because of background signals from intrinsic water protons. On the other hand, it is assumed that the <sup>11</sup>B NMR signals which can be applied to a CSI technique have certain advantages, since boron is an ultratrace element in animal cells and tissues. In this manuscript, we report on the sensing of biologically indispensable d-block metal cations such as zinc, copper, iron, cobalt, manganese, and nickel based on <sup>11</sup>B NMR signals of simple phenylboronic acid-pendant cyclen (cyclen = 1,4,7,10-tetraazacyclododecane), L<sup>6</sup> and L<sup>7</sup>, in aqueous solution at physiological pH. The results indicate that the carbon–boron bond of L<sup>6</sup> is cleaved upon the addition of Zn<sup>2+</sup> and the broad <sup>11</sup>B NMR signal of L<sup>6</sup> at 31 ppm is shifted upfield to 19 ppm, which corresponds to the signal of B(OH)<sub>3</sub>. <sup>1</sup>H NMR, X-ray single crystal structure analysis, and UV absorption spectra also provide support for the carbon–boron bond cleavage of ZnL<sup>6</sup>. Because the cellular uptake of L<sup>6</sup> was very small, a more cell-membrane permeable ligand containing the boronic acid ester L<sup>7</sup> was synthesized and investigated for the sensing of d-block metal ions using <sup>11</sup>B NMR. Data on <sup>11</sup>B NMR sensing of Zn<sup>2+</sup> in Jurkat T cells using L<sup>7</sup> is also presented
Design and Synthesis of Amphiphilic and Luminescent Tris-Cyclometalated Iridium(III) Complexes Containing Cationic Peptides as Inducers and Detectors of Cell Death via a Calcium-Dependent Pathway
Cationic amphiphilic peptides have
the potential to function as
agents for the treatment of microbial infections and cancer therapy.
The cationic and hydrophobic parts of these molecules allow them to
associate strongly with negatively charged bacterial or cancer cell
membranes, thus exerting antimicrobial and anticancer activities through
membrane disruption. Meanwhile, cyclometalated iridiumÂ(III) complexes
such as <i>fac</i>-IrÂ(ppy)<sub>3</sub> (ppy = 2-phenylpyridine)
and <i>fac</i>-IrÂ(tpy)<sub>3</sub> (tpy = 2-(4′-tolyl)Âpyridine)
possess <i>C</i><sub>3</sub>-symmetric structures and excellent
photophysical properties as phosphorescence materials, which make
them important candidates for use in biological applications such
as chemosensors, biolabeling, living cell staining, in vivo tumor
imaging, and anticancer agents. We recently reported on some regioselective
substitution reactions of IrÂ(tpy)<sub>3</sub> and IrÂ(ppy)<sub>3</sub> at the 5′-position (<i>p</i>-position with respect
to the C–Ir bond) on the 2-phenylpyridine ligands and their
subsequent conversions to a variety of functional groups. We report
here on the design and synthesis of amphiphilic and luminescent tris-cyclometalated
Ir complexes in which cationic peptides are attached through alkyl
chain linkers that work as inducers and detectors of cell death. Ir
complexes containing cationic peptides such as a KKGG sequence and
alkyl chain linkers of adequate length (C6 and C8) exhibit considerable
cytotoxicity against cancer cells such as Jurkat, Molt-4, HeLa-S3,
and A549 cells, and that dead cells are well stained with these Ir
complexes. Furthermore, an Ir complex in which the KKGG peptide is
attached through a C6 linker displayed lower cytotoxicity against
normal mouse lymphocytes. Mechanistic studies suggest that Ir complexes
containing the KKGG peptide interact with anionic molecules on the
cell surface and/or membrane receptors to trigger the Ca<sup>2+</sup> dependent pathway and intracellular Ca<sup>2+</sup> response, resulting
in necrosis accompanied by membrane disruption
Design and Synthesis of a Luminescent Cyclometalated Iridium(III) Complex Having <i>N</i>,<i>N</i>‑Diethylamino Group that Stains Acidic Intracellular Organelles and Induces Cell Death by Photoirradiation
Cyclometalated iridiumÂ(III) complexes have received considerable
attention and are important candidates for use as luminescent probes
for cellular imaging because of their potential photophysical properties.
We previously reported that <i>fac</i>-IrÂ(atpy)<sub>3</sub> <b>4</b> (atpy = 2-(5′-amino-4′-tolyl)Âpyridine)
containing three amino groups at the 5′-position of the atpy
ligand shows a maximum red emission (at around 600 nm) under neutral
and basic conditions and a green emission (at 531 nm) at acidic pH
(pH 3–4). In this Article, we report on the design and synthesis
of a new pH-sensitive cyclometalated IrÂ(III) complex containing a
2-(5′-<i>N</i>,<i>N</i>-diethylamino-4′-tolyl)Âpyridine
(deatpy) ligand, <i>fac</i>-IrÂ(deatpy)<sub>3</sub> <b>5</b>. The complex exhibits a considerable change in emission
intensity between neutral and slightly acidic pH (pH 6.5–7.4).
Luminescence microscopic studies using HeLa-S3 cells indicate that <b>5</b> can be used to selectively stain lysosome, an acidic organelle
in cells. Moreover, complex <b>5</b> is capable of generating
singlet oxygen in a pH-dependent manner and inducing the death of
HeLa-S3 cells upon photoirradiation at 377 or 470 nm
Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III) Complexes Having Basic and Nitro Groups and Application to pH Sensing and Photoinduced Cell Death
Cyclometalated
iridiumÂ(III) complexes, because of their photophysical
properties, have the potential for use as luminescent probes for cellular
imaging. We previously reported on a pH-activatable iridium complex
that contains three <i>N</i>,<i>N</i>-diethylamino
groups, namely, <i>fac</i>-IrÂ(deatpy)<sub>3</sub> <b>5</b>, which was synthesized via a regioselective aromatic substitution
reaction at the 5′-position with tolylpyridine groups of <i>fac</i>-IrÂ(tpy)<sub>3</sub> <b>2</b>. It was found that <b>5</b> shows a considerable enhancement in emission intensity in
the pH range from neutral to slightly acidic (pH 6.5–7.4) in
aqueous solution and selectively stains lysosome in HeLa-S3 cells,
due to the protonation of the diethylamino groups. In addition, <b>5</b> functions as a pH-dependent singlet oxygen (<sup>1</sup>O<sub>2</sub>) generator and induces necrosis-like cell death. However,
observing the green emission of <b>5</b> is often hampered by
autofluorescence emanating from nearby tissues. To overcome this problem,
we designed and synthesized a series of new pH-activatable IrÂ(III)
complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl
groups on the mpiq ligand of IrÂ(mpiq)<sub>3</sub> <b>7</b> and
the tfpiq ligand of IrÂ(tfpiq)<sub>3</sub> <b>8</b>, which exhibit
a red emission, namely, IrÂ(deampiq)<sub>3</sub> <b>13</b>, IrÂ(gmpiq)<sub>3</sub> <b>14</b>, IrÂ(imzmpiq)<sub>3</sub> <b>15</b>,
and IrÂ(imztfpiq)<sub>3</sub> <b>16</b>. The emission intensity
of these Ir complexes is enhanced substantially by protonation of
their basic groups, and they induce the necrosis-like cell death of
HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission
of IrÂ(mpiq-NO<sub>2</sub>)<sub>3</sub> <b>9</b> and IrÂ(tfpiq-NO<sub>2</sub>)<sub>3</sub> <b>10</b> is also reported
Efficient Synthesis of Tris-Heteroleptic Iridium(III) Complexes Based on the Zn<sup>2+</sup>-Promoted Degradation of Tris-Cyclometalated Iridium(III) Complexes and Their Photophysical Properties
We
report on the efficient synthesis of tris-heteroleptic iridium
(Ir) complexes based on the degradation of tris-cyclometalated Ir
complexes (IrL<sub>3</sub>, L: cyclometalating ligand) in the presence
of Brønsted and Lewis acids such as HCl (in 1,4-dioxane), AlCl<sub>3</sub>, TMSCl, and ZnX<sub>2</sub> (X = Br or Cl), which affords
the corresponding halogen-bridged Ir dimers (ÎĽ-complexes). Tris-cyclometalated
Ir complexes containing electron-withdrawing groups such as fluorine,
nitro, or CF<sub>3</sub> moieties on the ligands were less reactive.
This different reactivity was applied to the selective degradation
of heteroleptic Ir complexes such as <i>fac</i>-IrÂ(tpy)<sub>2</sub>(F<sub>2</sub>ppy) (<i><b>fac</b></i><b>-12</b>) (tpy: 2-(4′-tolyl)Âpyridine and F<sub>2</sub>ppy:
2-(4′,6′-difluorophenyl)Âpyridine), <i>mer</i>-IrÂ(tpy)<sub>2</sub>(F<sub>2</sub>ppy) (<i><b>mer</b></i><b>-12</b>), and <i>mer</i>-IrÂ(mpiq)<sub>2</sub>(F<sub>2</sub>ppy) (<i><b>mer</b></i><b>-15</b>) (mpiq:
1-(4′-methylphenyl)Âisoquinoline). For example, the reaction
of <i><b>mer</b></i><b>-12</b> with ZnBr<sub>2</sub> gave the heteroleptic ÎĽ-complex [{IrÂ(tpy)Â(F<sub>2</sub>ppy)Â(ÎĽ-Br)}<sub>2</sub>] <b>27b</b> as a major product,
resulting from the selective elimination of the tpy ligand of <i><b>mer</b></i><b>-12</b>, and treatment of <b>27b</b> with acetylacetone (acacH) afforded the corresponding
tris-heteroleptic Ir complex IrÂ(tpy)Â(F<sub>2</sub>ppy)Â(acac)<b>18</b>. In addition, another tris-heteroleptic Ir complex <b>35a</b> having 8-benzeneÂsulfonylÂamidoÂquinoline
(8BSQ) ligand was synthesized. Mechanistic studies of this degradation
reaction and the photochemical properties, especially a dual emission,
of these newly synthesized tris-heteroleptic Ir complexes are also
reported
Stereospecific Synthesis of Tris-heteroleptic Tris-cyclometalated Iridium(III) Complexes via Different Heteroleptic Halogen-Bridged Iridium(III) Dimers and Their Photophysical Properties
Herein,
we report on the stereospecific synthesis of two single
isomers of tris-heteroleptic tris-cyclometalated iridiumÂ(III) (IrÂ(III))
complexes composed of three different nonsymmetric cyclometalating
ligands via heteroleptic halogen-bridged Ir dimers [IrÂ(tpy)Â(F<sub>2</sub>ppy)Â(ÎĽ-Br)]<sub>2</sub> <b>17b</b> and [IrÂ(mpiq)Â(F<sub>2</sub>ppy)Â(ÎĽ-Br)]<sub>2</sub> <b>27b</b> (tpyH:
(2-(4′-tolyl)ÂpyriÂdine) and F<sub>2</sub>ppyH: (2-(4′,6′-diÂfluoroÂphenyl)Âpyridine),
and mpiqH: (1-(4′-methylÂphenyl)ÂisoÂquinoline))
prepared by Zn<sup>2+</sup>-promoted degradation of IrÂ(tpy)<sub>2</sub>Â(F<sub>2</sub>ppy) <b>21</b> and IrÂ(mpiq)<sub>2</sub>Â(F<sub>2</sub>ppy) <b>26</b>, as reported by us.
Subsequently, <b>17b</b> and <b>27b</b> were converted
to the tris-heteroleptic tris-cyclometalated Ir complexes IrÂ(tpy)Â(F<sub>2</sub>ppy)Â(mpiq) <b>25</b> consisting of tpy, F<sub>2</sub>ppy, and mpiq, as confirmed by spectroscopic data and X-ray
crystal structure analysis. The first important point in this work
is the selective synthesis of specific isomers among eight possible
stereoisomers of Ir complexes having the same combination of three
cyclometalating ligands. Namely, two meridional forms of <b>25</b> were synthesized and isolated. The second finding is that the different
stereoisomers of <b>25</b> have different stability. Finally,
different stereoisomers exhibit different emission spectra. Namely,
one of its stereoisomers <b>25a</b> exhibits a single broad
emission from <i>ca</i>. 550 nm to <i>ca</i>.
650 nm (orange emission), while stereoisomer <b>25c</b> emits
dual emission at <i>ca</i>. 509 nm and <i>ca</i>. 600 nm (pale pink emission), as supported by time-dependent density
functional theory calculation. To the best of our knowledge, this
is the first report of the selective and efficient synthesis of different
stereoisomers of tris-heteroleptic tris-cyclometalated IrÂ(III) complexes
that have different stabilities and different photophysical properties