The sensitivity of both nuclear magnetic resonance spectroscopy and magnetic resonance imaging is very low because the detected signal strength depends on the small population difference between spin ...states even in high magnetic fields. Hyperpolarization methods can be used to increase this difference and thereby enhance signal strength. This has been achieved previously by incorporating the molecular spin singlet para-hydrogen into hydrogenation reaction products. We show here that a metal complex can facilitate the reversible interaction of para-hydrogen with a suitable organic substrate such that up to an 800-fold increase in proton, carbon, and nitrogen signal strengths are seen for the substrate without its hydrogenation. These polarized signals can be selectively detected when combined with methods that suppress background signals.
Cellular uptake, luminescence imaging and antimicrobial activity against clinically relevant methicillin-resistant
S. aureus
(MRSA) bacteria are reported. The osmium(
ii
) complexes Os(
N
^
N
)
3
2+
...(
N
^
N
= 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole (
1
2+
); 1-benzyl-4-(pyrimidin-2-yl)-1,2,3-triazole (
2
2+
); 1-benzyl-4-(pyrazin-2-yl)-1,2,3-triazole (
3
2+
)) were prepared and isolated as the chloride salts of their meridional and facial isomers. The complexes display prominent spin-forbidden ground state to triplet metal-to-ligand charge transfer (
3
MLCT) state absorption bands enabling excitation as low as 600 nm for
fac
/
mer
-
3
2+
and observation of emission in aqueous solution in the deep-red/near-IR regions of the spectrum. Cellular uptake studies within MRSA cells show antimicrobial activity for
1
2+
and
2
2+
with greater toxicity for the meridional isomers in each case and
mer
-
1
2+
showing the greatest potency (32 μg mL
−1
in defined minimal media). Super-resolution imaging experiments demonstrate binding of
mer
- and
fac
-
1
2+
to bacterial DNA with high Pearson's colocalisation coefficients (up to 0.95 using DAPI). Phototoxicity studies showed the complexes exhibited a higher antimicrobial activity upon irradiation with light.
Cellular uptake, luminescence imaging and antimicrobial activity of facial and meridional isomers of Os(
ii
) triazole-based complexes against methicillin-resistant
S. aureus
, MRSA.
Fundamental insights into the mechanism of triplet-excited-state interligand energy transfer dynamics and the origin of dual emission for phosphorescent iridium(III) complexes are presented. The ...complexes Ir(C∧N)2(N∧N)+ (HC∧N = 2-phenylpyridine (1a–c), 2-(2,4-difluorophenyl)pyridine (2a–c), 1-benzyl-4-phenyl-1,2,3-triazole (3a–c); N∧N = 1-benzyl-4-(pyrid-2-yl)-1,2,3-triazole (pytz, a), 1-benzyl-4-(pyrimidin-2-yl)-1,2,3-triazole (pymtz, b), 1-benzyl-4-(pyrazin-2-yl)-1,2,3-triazole (pyztz, c)) are phosphorescent in room-temperature fluid solutions from triplet metal-to-ligand charge transfer (3MLCT) states admixed with either ligand-centered (3LC) (1a, 2a, and 2b) or ligand-to-ligand charge transfer (3LL′CT) character (1c, 2c, and 3a–c). Particularly striking is the observation that pyrimidine-based complex 1b exhibits dual emission from both 3MLCT/3LC and 3MLCT/3LL′CT states. At 77 K, the 3MLCT/3LL′CT component is lost from the photoluminescence spectra of 1b, with emission exclusively arising from its 3MLCT/3LC state, while for 2c switching from 3MLCT/3LL′CT- to 3MLCT/3LC-based emission is observed. Femtosecond transient absorption data reveal distinct spectral signatures characteristic of the population of 3MLCT/3LC states for 1a, 2a, and 2b which persist throughout the 3 ns time frame of the experiment. These 3MLCT/3LC state signatures are apparent in the transient absorption spectra for 1c and 2c immediately following photoexcitation but rapidly evolve to yield spectral profiles characteristic of their 3MLCT/3LL′CT states. Transient data for 1b reveals intermediate behavior: the spectral features of the initially populated 3MLCT/3LC state also undergo rapid evolution, although to a lesser extent than that observed for 1c and 2c, behavior assigned to the equilibration of the 3MLCT/3LC and 3MLCT/3LL′CT states. Density functional theory (DFT) calculations enabled minima to be optimized for both 3MLCT/3LC and 3MLCT/3LL′CT states of 1a–c and 2a–c. Indeed, two distinct 3MLCT/3LC minima were optimized for 1a, 1b, 2a, and 2b distinguished by upon which of the two C∧N ligands the excited electron resides. The 3MLCT/3LC and 3MLCT/3LL′CT states for 1b are very close in energy, in excellent agreement with experimental data demonstrating dual emission. Calculated vibrationally resolved emission spectra (VRES) for the complexes are in excellent agreement with experimental data, with the overlay of spectral maxima arising from emission from the 3MLCT/3LC and 3MLCT/3LL′CT states of 1b convincingly reproducing the observed experimental spectral features. Analysis of the optimized excited-state geometries enable the key structural differences between the 3MLCT/3LC and 3MLCT/3LL′CT states of the complexes to be identified and quantified. The calculation of interconversion pathways between triplet excited states provides for the first time a through-space mechanism for a photoinduced interligand energy transfer process. Furthermore, examination of structural changes between the possible emitting triplet excited states reveals the key bond vibrations that mediate energy transfer between these states. This work therefore provides for the first time detailed mechanistic insights into the fundamental photophysical processes of this important class of complexes.
Diimine metal complexes have significant relevance in the development of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) applications. In particular, complexes of the TAP ligand ...(1,4,5,8-tetraazaphenanthrene) are known to lead to photoinduced oxidation of DNA, while TAP- and triazole-based complexes are also known to undergo photochemical ligand release processes relevant to PACT. The photophysical and photochemical properties of heteroleptic complexes Ru(TAP) n (btz)3–n 2+ (btz = 1,1′-dibenzyl-4,4′-bi-1,2,3-triazolyl, n = 1 (1), 2 (2)) have been explored. Upon irradiation in acetonitrile, 1 displays analogous photochemistry to that previously observed for Ru(bpy)(btz)22+ (bpy = 2,2′-bipyridyl) and generates trans-Ru(TAP)(btz)(NCMe)22+ (5), which has been crystallographically characterized, with the observation of the ligand-loss intermediate trans-Ru(TAP)(κ2-btz)(κ1-btz)(NCMe)2+ (4). Complex 2 displays more complicated photochemical behavior with not only preferential photorelease of btz to form cis-Ru(TAP)2(NCMe)22+ (6) but also competitive photorelease of TAP to form 5. Free TAP is then taken up by 6 to form Ru(TAP)32+ (3) with the proportion of 5 and 3 observed to progressively increase during prolonged photolysis. Data suggest a complex set of reversible photochemical ligand scrambling processes in which 2 and 3 are interconverted. Computational DFT calculations have enabled optimization of geometries of the pro-trans 3MC cis states with repelled btz or TAP ligands crucial for the formation of 5 from 1 and 2, respectively, lending weight to recent evidence that such 3MC cis states play an important mechanistic role in the rich photoreactivity of Ru(II) diimine complexes.
In a systematic survey of luminescent bis(terdentate) osmium(II) complexes, a tipping point involving a reversal in photophysical tuning is observed whereby increasing stabilization of the ...ligand-based lowest unoccupied molecular orbital (LUMO) results in a blue shift in the optical absorption and emission bands. The complexes Os(N^N′^N″)22+ N^N′^N″ = 2,6-bis(1-phenyl-1,2,3-triazol-4-yl)pyridine (Os1), 2,6-bis(1-benzyl-1,2,3-triazol-4-yl)pyrazine (Os2), 6-(1-benzyl-1,2,3-triazol-4-yl)-2,2′-bipyridyl (Os3), 2-(pyrid-2-yl)-6-(1-benzyl-1,2,3-triazol-4-yl)pyrazine (Os4), 2-(pyrazin-2-yl)-6-(1-benzyl-1,2,3-triazol-4-yl)pyridine (Os5), and 6-(1-benzyl-1,2,3-triazol-4-yl)-2,2′-bipyrazinyl (Os6) have been prepared and characterized, and all complexes display phosphorescence ranging from the orange to near-IR regions of the spectrum. Replacement of the central pyridine in the ligands of Os1 by the more π-accepting pyrazine in Os2 results in a 55 nm red shift in the triplet metal-to-ligand charge-transfer-based emission band, while a larger red shift of 107 nm is observed for the replacement of one of the triazole donors in the ligands of Os1 by a second pyridine ring in Os3 (λem max = 702 nm). Interestingly, replacement of the central pyridine ring in the ligands of Os3 by pyrazine (Os4, λem max = 702 nm) fails to result in a further red shift in the emission band. Reversal of the relative positions of the pyridine and pyrazine donors in Os5 (λem max = 733 nm) compared to Os4 does indeed result in the expected red shift in the emission with respect to that for Os3 based on the increased π-acceptor character of the ligands present. However, an inversion in emission tuning is observed for Os6, in which the incorporation of a second pyrazine donor in the ligand architecture results in a blue shift in the optical absorption and emission maxima (λem max = 710 nm). Electrochemical studies reveal that while incorporating pyrazine in the ligands indeed results in an expected anodic shift in the first reduction potential through stabilization of the ligand-based LUMO, there is also a concomitant anodic shift in the OsII/OsIII-based oxidation potential. This stabilization of the metal-based highest occupied molecular orbital (HOMO) thus nullifies the effect of stabilization of the LUMO in Os4 compared to Os3, resulting in these complexes having coincident emission maxima. For Os6, stabilization of the HOMO through the incorporation of two pyrazine donors in the ligand structure now exceeds stabilization of the LUMO, resulting in a larger HOMO–LUMO gap and a counterintuitive blue shift in the optical properties in comparison with those of Os5. While it is known that the replacement of ligands (e.g., replacing bipyridyl with bipyrazinyl) can result in a larger HOMO–LUMO energy gap through greater stabilization of the HOMO, these results importantly allow us to capture the tipping point at which this inversion in photophysical tuning occurs. This therefore enables us to explore the limits available in emission tuning with a relatively simple and minimalist ligand structure.
Photochemical ligand release from metal complexes may be exploited in the development of novel photoactivated chemotherapy agents for the treatment of cancer and other diseases. Highly intriguing ...photochemical behavior is reported for two ruthenium(II) complexes bearing conformationally flexible 1,2,3-triazole-based ligands incorporating a methylene spacer to form 6-membered chelate rings. Ru(bpy)2(pictz)2+ (1) and Ru(bpy)2(btzm)2+ (2) (bpy = 2,2′-bipyridyl; pictz = 1-(picolyl)-4-phenyl-1,2,3-triazole; btzm = bis(4-phenyl-1,2,3-triazol-4-yl)methane) exhibit coordination by the triazole ring through the less basic N2 atom as a consequence of chelation and readily undergo photochemical release of the pictz and btzm ligands (ϕ = 0.079 and 0.091, respectively) in acetonitrile solution to form cis-Ru(bpy)2(NCMe)22+ (3) in both cases. Ligand-loss intermediates of the form Ru(bpy)2(κ1-pictz or κ1-btzm)(NCCD3)2+ are detected by 1H NMR spectroscopy and mass spectrometry. Photolysis of 1 yields three ligand-loss intermediates with monodentate pictz ligands, two of which form through simple decoordination of either the pyridine or triazole donor with subsequent solvent coordination (4-tz (N2) and 4-py, respectively). The third intermediate, shown to be able to form photochemically directly from 1, arises through linkage isomerism in which the monodentate pictz ligand is coordinated by the triazole N3 atom (4-tz (N3) ) with a comparable ligand-loss intermediate with an N3-bound κ1-btzm ligand also observed for 2.
The ligands L1 and L2 both form separable dinuclear double‐stranded helicate and mesocate complexes with RuII. In contrast to clinically approved platinates, the helicate isomer of Ru2(L1)24+ was ...preferentially cytotoxic to isogenic cells (HCT116 p53−/−), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53+/+. Other structurally similar RuII‐containing dinuclear complexes showed very little cytotoxic activity. This study demonstrates that alterations in ligand or isomer can have profound effects on cytotoxicity towards cancer cells of different p53 status and suggests that selectivity can be “tuned” to either genotype. In the search for compounds that can target difficult‐to‐treat tumours that lack the p53 tumour suppressor gene, Ru2(L1)24+ is a promising compound for further development.
Cell‐selective: The bis‐tridentate ligand L1 forms both the dinuclear double helicate and mesocate upon reaction with ruthenium(II). Cytotoxicity studies show that the helicate is selective to HCT116 p53−/− cancer cells whereas the mesocate is selective to HCT116 p53+/+.
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