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1.
Biochemistry ; 62(10): 1531-1543, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37115010

RESUMO

Lipoxygenase (LOX) enzymes produce important cell-signaling mediators, yet attempts to capture and characterize LOX-substrate complexes by X-ray co-crystallography are commonly unsuccessful, requiring development of alternative structural methods. We previously reported the structure of the complex of soybean lipoxygenase, SLO, with substrate linoleic acid (LA), as visualized through the integration of 13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) computations. However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ ion as a spin probe. Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear Mn2+ metallocenters. Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX from rice blast pathogen Magnaporthe oryzae, MoLOX complexed with LA, as obtained through the 13C/1H ENDOR-guided MD approach. The catalytically important distance between the hydrogen donor, carbon-11 (C11), and the acceptor, Mn-bound oxygen, (donor-acceptor distance, DAD) for the MoLOX-LA complex derived in this fashion is 3.4 ± 0.1 Å. The difference of the MoLOX-LA DAD from that of the SLO-LA complex, 3.1 ± 0.1 Å, is functionally important, although is only 0.3 Å, despite the MoLOX complex having a Mn-C11 distance of 5.4 Å and a "carboxylate-out" substrate-binding orientation, whereas the SLO complex has a 4.9 Å Mn-C11 distance and a "carboxylate-in" substrate orientation. The results provide structural insights into reactivity differences across the LOX family, give a foundation for guiding development of MoLOX inhibitors, and highlight the robustness of the ENDOR-guided MD approach to describe LOX-substrate structures.


Assuntos
Lipoxigenase , Simulação de Dinâmica Molecular , Animais , Lipoxigenase/química , Espectroscopia de Ressonância de Spin Eletrônica , Hidrogênio/química , Ácido Linoleico/química
2.
Dalton Trans ; 51(36): 13858-13866, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36040117

RESUMO

The synthesis, photophysics, and electrochemiluminescence (ECL) of four water-soluble dinuclear Ir(III) and Ru(II) complexes (1-4) terminally-capped by 4'-phenyl-2,2':6',2''-terpyridine (tpy) or 1,3-di(pyrid-2-yl)-4,6-dimethylbenzene (N^C^N) ligands and linked by a 2,7-bis(2,2':6',2''-terpyridyl)fluorene with oligoether chains on C9 are reported. The impact of the tpy or N^C^N ligands and metal centers on the photophysical properties of 1-4 was assessed by spectroscopic methods including UV-vis absorption, emission, and transient absorption, and by time-dependent density functional theory (TDDFT) calculations. These complexes exhibited distinct singlet and triplet excited-state properties upon variation of the terminal-capping terdentate ligands and the metal centers. The ECL properties of complexes 1-3 with better water solubility were investigated in neutral phosphate buffer solutions (PBS) by adding tripropylamine (TPA) as a co-reactant, and the observed ECL intensity followed the descending order of 3 > 1 > 2. Complex 3 bearing the [Ru(tpy)2]2+ units displayed more pronounced ECL signals, giving its analogues great potential for further ECL study.

3.
J Phys Chem Lett ; 13(6): 1416-1423, 2022 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-35119280

RESUMO

Semiconductor nanocrystals (NCs) have emerged as promising photocatalysts. However, NCs are often functionalized with complex ligand shells that contain not only charge acceptors but also other "spectator ligands" that control NC solubility and affinity for target reactants. Here, we show that spectator ligands are not passive observers of photoinduced charge transfer but rather play an active role in this process. We find the rate of electron transfer from quantum-confined PbS NCs to perylenediimide acceptors can be varied by over a factor of 4 simply by coordinating cinnamate ligands with distinct dipole moments to NC surfaces. Theoretical calculations indicate this rate variation stems from both ligand-induced changes in the free energy for charge transfer and electrostatic interactions that alter perylenediimide electron acceptor orientation on NC surfaces. Our work shows NC-to-molecule charge transfer can be fine-tuned through ligand shell design, giving researchers an additional handle for enhancing NC photocatalysis.

4.
J Phys Chem A ; 125(1): 74-87, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33389995

RESUMO

We investigate (1) electron-beam-induced plasmon absorption spectra of Ag molecular nanowire dimers and (2) electron-beam-induced energy transfer between two nanowires. We employ linear-response time-dependent density functional theory (TDDFT) and real-time TDDFT methods to simulate the electron-beam-induced plasmonic excitations, dynamics, and corresponding electron energy loss spectrum for small models of a single molecular nanowire with four Ag atoms and for two Ag nanowires. An array of different relative orientations of nanowires and of different initial excitation conditions resulting from applying an electron beam at different positions with respect to the Ag nanowires is investigated. The results demonstrate (1) an electron beam can induce plasmonic excitations from the molecular Ag nanowire ground state to the excited states that are both optically allowed and forbidden, (2) a tunability for selective excitations that can be controlled by the position of a focused electron beam, and (3) kinetic and dynamic behaviors of time-dependent electron-beam-induced energy transfer between two Ag molecular nanowires depend on the position of the beam source and nanowire separation distance, providing insights into the spatial dependences of plasmonic couplings in nanowire arrays.

5.
J Phys Chem A ; 124(43): 8931-8942, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33079551

RESUMO

DNA-wrapped silver nanoclusters (DNA-AgNCs) are known for their efficient luminescence. However, their emission is highly sensitive to the DNA sequence, the cluster size, and its charge state. To get better insights into photophysics of these hybrid systems, simulations based on density functional theory (DFT) are performed. Our calculations elucidate the effect of the structural conformations, charges, solvent polarity, and passivating bases on optical spectra of DNA-AgNCs containing five and six Ag atoms. It is found that inclusion of water in calculations as a polar solvent media results in stabilization of nonplanar conformations of base-passivated clusters, while their planar conformations are more stable in vacuum, similar to the bare Ag5 and Ag6 clusters. Cytosines and guanines interact with the cluster twice stronger than thymines, due to their larger dipole moments. In addition to the base-cluster interactions, hydrogen bonds between bases notably contribute to the structure stabilization. While the relative intensity, line width, and the energy of absorption peaks are slightly changing depending on the cluster charge, conformations, and base types, the overall spectral shape with five well-resolved bands at 2.5-5.5 eV is consistent for all structures. Independent of the passivating bases and the cluster size and charge, the low energy optical transitions at 2.5-3.5 eV exhibit a metal to ligand charge transfer (MLCT) character with the main contribution emerging from Ag-core to the bases. Cytosines facilitate the MLCT character to a larger degree comparing to the other bases. However, the doublet transitions in clusters with the open shell electronic structure (Ag5 and Ag6+) result in appearance of additional red-shifted (<2.5 eV) and optically weak band with negligible MLCT character. The passivated clusters with the closed shell electronic structure (Ag5+ and Ag6) exhibit higher optical intensity of their lowest transitions with much higher MLCT contribution, thus having better potential for emission, than their open shell counterparts.

6.
Inorg Chem ; 59(12): 8532-8542, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32497429

RESUMO

Extending the bandwidth of triplet excited-state absorption in transition-metal complexes is appealing for developing broadband reverse saturable absorbers. Targeting this goal, five bis-terdentate iridium(III) complexes (Ir1-Ir5) bearing trans-bis-cyclometalating (C^N^C) and 4'-R-2,2':6',2″-terpyridine (4'-R-tpy) ligands were synthesized. The effects of the structural variation in cyclometalating ligands and substituents at the tpy ligand on the photophysics of these complexes have been systematically explored using spectroscopic methods (i.e., UV-vis absorption, emission, and transient absorption spectroscopy) and time-dependent density functional theory (TDDFT) calculations. All complexes exhibited intensely structured 1π,π* absorption bands at <400 nm and broad charge transfer (1CT)/1π,π* transitions at 400-600 nm. Ligand structural variations exerted a very small effect on the energies of the 1CT/1π,π* transitions; however, they had a significant effect on the molar extinction coefficients of these absorption bands. All complexes emitted featureless deep red phosphorescence in solutions at room temperature and gave broad-band and strong triplet excited-state absorption ranging from the visible to the near-infrared (NIR) spectral regions, with both originating from the 3π,π*/3CT states. Although alteration of the ligand structures influenced the emission energies slightly, these changes significantly affected the emission lifetimes and quantum yields, transient absorption spectral features, and the triplet excited-state quantum yields of the complexes. Except for Ir3, the other four complexes all manifested reverse saturable absorption (RSA) upon nanosecond laser pulse excitation at 532 nm, with the decreasing trend of RSA following Ir2 ≈ Ir4 > Ir1 > Ir5 > Ir3. The RSA trend corresponded well with the strength of the excited-state and ground-state absorption differences (ΔOD) at 532 nm for these complexes.

7.
ACS Appl Bio Mater ; 3(9): 6025-6038, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-35021831

RESUMO

Three heteroleptic bis-terpyridine ruthenium(II) complexes (Ru1-Ru3) [Ru(tpy-R1)(tpy-R2)]2+ (tpy = 2,2':6',2″-terpyridine, R1/R2 = phenyl, 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}phenyl, pyren-1-yl, or 4-phenyl-BODIPY (boron dipyrromethene)) were synthesized and investigated for their potential applications as photosensitizers (PSs) for photodynamic therapy. All complexes displayed broad and intense absorption band in the green spectral regions (450-600 nm), which arose from the spin-allowed charge-transfer transitions mixed with ligand-localized 1π,π* transitions. All complexes show weak green emission at 513-549 nm and/or even weaker red emission at 646-674 nm at room temperature depending on the excitation wavelength and the solvent used. Incorporating the BODIPY motif to the 4'-position of one of the tpy ligands in Ru2 and Ru3 drastically prolonged the lifetimes of the lowest triplet excited states (T1) of Ru2 and Ru3 to tens of microseconds. This promoted the singlet oxygen formation sensitized by Ru2 and Ru3 upon green light activation, which in turn induced significant photocytotoxicity toward the A549 human lung cancer cell line with an EC50 value of 1.50 µM for Ru2 and 7.41 µM for Ru3 under 0.48 J·cm-2 500 nm light irradiation. Laser confocal scanning microscopy imaging revealed that Ru2 mainly distributed to lysosomes upon cell uptake. Upon 500 nm light activation, Ru2 induced lysosomal damage and subsequent mitochondrial membrane potential decrease. The dominant cell death pathway was apoptosis. These results demonstrated the potential utilization of [Ru(tpy-R1)(tpy-R2)]2+ complexes as PSs for PDT.

8.
ACS Appl Bio Mater ; 2(7): 2964-2977, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31844844

RESUMO

Six homo- or heteroleptic tricationic Ir(R1-tpy)(R2-tpy)3+ complexes (Ir1-Ir6, R1/R2 = Ph, 4'-N(CH3)2Ph, pyren-1-yl, or 4'-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy}Ph, tpy = 2,2';6',2"-terpyridine) were synthesized and tested for photodynamic therapy (PDT) effects. The ground- and excited-state characteristics of these complexes were studied systematically via spectroscopic methods and quantum chemistry calculations. All complexes possessed intraligand charge transfer (1ILCT) / metal-to-ligand charge transfer (1MLCT) dominated transition(s) in their low-energy absorption bands, which red-shifted with the increased electron-releasing strength of the R1/R2 substituent. Five of the complexes exhibited ligand-centered 3 π,π*/3ILCT/3MLCT emission. With a stronger electron-releasing R1/R2 substituent, the degree of charge transfer contribution increased, leading to a decrease of the emission quantum yield. When the 4'-N(CH3)2Ph substituent was introduced on both tpy ligands, the emission of Ir3 was completely quenched. Our study on the transient absorption of these complexes demonstrated that they all possessed broadband triplet excited-state absorption in the 400-800 nm region. Pyrenyl substitution of one or more tpy ligands, as in Ir4 and Ir5, increased the lifetimes of the lowest triplet excited state and the singlet oxygen (1O2) production efficiencies. Ir1-Ir5 were nontoxic toward SK-MEL-28 cells, with photocytotoxicities that varied from 0.18 to 153 µM. Among them, Ir4 had the highest 1O2 quantum yield (0.81) in cell-free conditions, showing the largest photocytotoxicity against SK-MEL-28 cells for Ir(III) PSs to date, and was the most efficient generator of reactive oxygen species (ROS) in vitro. Ir4 possessed a very large phototherapeutic index (PI = dark EC50 / light EC50) of >1657, the largest reported for an Ir(III) complex photosensitizer upon broadband visible light (400-700 nm) activation. Ir4 also exhibited a very strong PDT effect toward MCF-7 breast cancer cells and its xenograft tumor model. Upon 450-nm light activation, Ir4 dramatically inhibited the xenograft tumor growth and exhibited negligible side effects upon PDT treatment.

9.
Inorg Chem ; 58(21): 14377-14388, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31625389

RESUMO

The synthesis, crystal structure, and photophysics of a series of neutral cyclometalated iridium(III) complexes bearing substituted N-heterocyclic carbene (NHC) ancillary ligands ((C∧N)2Ir(R-NHC), where C∧N and NHC refer to the cyclometalating ligand benzo[h]quinoline and 1-phenylbenzimidazole, respectively) are reported. The NHC ligands were substituted with electron-withdrawing or -donating groups on C4' of the phenyl ring (R = NO2 (Ir1), CN (Ir2), H (Ir3), OCH3 (Ir4), N(CH3)2 (Ir5)) or C5 of the benzimidazole ring (R = NO2 (Ir6), N(CH3)2 (Ir7)). The configuration of Ir1 was confirmed by a single-crystal X-ray diffraction analysis. The ground- and excited-state properties of Ir1-Ir7 were investigated by both spectroscopic methods and time-dependent density functional theory (TDDFT) calculations. All complexes possessed moderately strong structureless absorption bands at ca. 440 nm that originated from the C∧N ligand based 1π,π*/1CT (charge transfer)/1d,d transitions and very weak spin-forbidden 3MLCT (metal-to-ligand charge transfer)/3LLCT (ligand-to-ligand charge transfer) transitions beyond 500 nm. Electron-withdrawing substituents caused a slight blue shift of the 1π,π*/1CT/1d,d band, while electron-donating substituents induced a red shift of this band in comparison to the unsubstituted complex Ir3. Except for the weakly emissive nitro-substituted complexes Ir1 and Ir6 that had much shorter lifetimes (≤160 ns), the other complexes are highly emissive in organic solutions with microsecond lifetimes at ca. 540-550 nm at room temperature, with the emitting states being predominantly assigned to 3π,π*/3MLCT states. Although the effect of the substituents on the emission energy was insignificant, the effects on the emission quantum yields and lifetimes were drastic. All complexes also exhibited broad triplet excited-state absorption at 460-700 nm with similar spectral features, indicating the similar parentage of the lowest triplet excited states. The highly emissive Ir2 was used as a dopant for organic light-emitting diode (OLED) fabrication. The device displayed a yellow emission with a maximum current efficiency (ηc) of 71.29 cd A-1, a maximum luminance (Lmax) of 32747 cd m-2, and a maximum external quantum efficiency (EQE) of 20.6%. These results suggest the potential of utilizing this type of neutral Ir(III) complex as an efficient yellow phosphorescent emitter.

10.
Photochem Photobiol Sci ; 18(10): 2381-2396, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31432864

RESUMO

The synthesis, photophysics, and photobiological activities of a series of novel neutral heteroleptic cyclometalated iridium(iii) complexes incorporating boron dipyrromethene (BODIPY) substituted N-heterocyclic carbene (NHC) ligands (Ir1-Ir5) are reported. The effect of the substitution position of BODIPY on the NHC ligands, either on C4 of the phenyl ring (Ir1-Ir3) or C5 of the benzimidazole unit (Ir4 and Ir5), and its linker type (single or triple bond) on the photophysical properties was studied. Ir1-Ir5 exhibited BODIPY-localized intense 1IL (intraligand transition)/1MLCT (metal-to-ligand charge transfer) absorption at 530-543 nm and 1,3IL/1,3CT (charge transfer) emission at 582-610 nm. The nanosecond transient absorption results revealed that the lowest triplet excited states of these complexes were the BODIPY-localized 3π,π* states. Complexes Ir4 and Ir5 exhibited blue-shifted 1IL absorption and 1,3IL/1,3CT emission bands compared to the corresponding absorption and emission bands in complexes Ir1 and Ir3. However, replacing the methyl substituents on N3 of benzimidazole in complexes Ir1 and Ir4 with oligoether substituents in Ir3 and Ir5, respectively, did not impact the energies of the low-energy absorption and emission bands in the corresponding complexes. Water-soluble complexes Ir3 and Ir5 have been explored as photosensitizers for in vitro photodynamic therapy (PDT) effects toward human SKMEL28 melanoma cells. Ir3 showed no dark cytotoxicity (EC50 > 300 µM) but good photocytotoxic activity (9.66 ± 0.28 µM), whereas Ir5 exhibited a higher dark cytotoxicity (20.2 ± 1.26 µM) and excellent photocytotoxicity (0.15 ± 0.01 µM). The phototherapeutic indices with visible light (400-700 nm) activation were >31 for Ir3 and 135 for Ir5. Ir3 and Ir5 displayed 1O2 quantum yields of 38% and 22% in CH3CN, respectively, upon 450 nm excitation. Ir5 was more effective at generating reactive oxygen species (ROS) in vitro. Ir5 was also active against Staphylococcus aureus upon visible light activation, with a phototherapeutic index of >15 and EC50 value of 6.67 µM. These photobiological activities demonstrated that these neutral Ir(iii) complexes are promising in vitro PDT reagents, and substitution at C5 on the benzimidazole group of the NHC ligand was superior to C4 substitution on the phenyl ring.


Assuntos
Compostos de Boro/química , Complexos de Coordenação/química , Irídio/química , Metano/análogos & derivados , Fármacos Fotossensibilizantes/síntese química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Humanos , Ligantes , Luz , Metano/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Teoria Quântica , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Nanomedicina Teranóstica
11.
Inorg Chem ; 56(6): 3245-3259, 2017 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-28263079

RESUMO

Five heteroleptic tris-diimine ruthenium(II) complexes [RuL(N^N)2](PF6)2 (where L is 3,8-di(benzothiazolylfluorenyl)-1,10-phenanthroline and N^N is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 1,4,8,9-tetraazatriphenylene (tatp) (3), dipyrido[3,2-a:2',3'-c]phenazine (dppz) (4), or benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn) (5), respectively) were synthesized. The influence of π-conjugation of the ancillary ligands (N^N) on the photophysical properties of the complexes was investigated by spectroscopic methods and simulated by density functional theory (DFT) and time-dependent DFT. Their ground-state absorption spectra were characterized by intense absorption bands below 350 nm (ligand L localized 1π,π* transitions) and a featureless band centered at ∼410 nm (intraligand charge transfer (1ILCT)/1π,π* transitions with minor contribution from metal-to-ligand charge transfer (1MLCT) transition). For complexes 4 and 5 with dppz and dppn ligands, respectively, broad but very weak absorption (ε < 800 M-1 cm-1) was present from 600 to 850 nm, likely emanating from the spin-forbidden transitions to the triplet excited states. All five complexes showed red-orange phosphorescence at room temperature in CH2Cl2 solution with decreased lifetimes and emission quantum yields, as the π-conjugation of the ancillary ligands increased. Transient absorption (TA) profiles were probed in acetonitrile solutions at room temperature for all of the complexes. Except for complex 5 (which showed dppn-localized 3π,π* absorption with a long lifetime of 41.2 µs), complexes 1-4 displayed similar TA spectral features but with much shorter triplet lifetimes (1-2 µs). Reverse saturable absorption (RSA) was demonstrated for the complexes at 532 nm using 4.1 ns laser pulses, and the strength of RSA decreased in the order: 2 ≥ 1 ≈ 5 > 3 > 4. Complex 5 is particularly attractive as a broadband reverse saturable absorber due to its wide optical window (430-850 nm) and long-lived triplet lifetime in addition to its strong RSA at 532 nm. Complexes 1-5 were also probed as photosensitizing agents for in vitro photodynamic therapy (PDT). Most of them showed a PDT effect, and 5 emerged as the most potent complex with red light (EC50 = 10 µM) and was highly photoselective for melanoma cells (selectivity factor, SF = 13). Complexes 1-5 were readily taken up by cells and tracked by their intracellular luminescence before and after a light treatment. Diagnostic intracellular luminescence increased with increased π-conjugation of the ancillary N^N ligands despite diminishing cell-free phosphorescence in that order. All of the complexes penetrated the nucleus and caused DNA condensation in cell-free conditions in a concentration-dependent manner, which was not influenced by the identity of N^N ligands. Although the mechanism for photobiological activity was not established, complexes 1-5 were shown to exhibit potential as theranostic agents. Together the RSA and PDT studies indicate that developing new agents with long intrinsic triplet lifetimes, high yields for triplet formation, and broad ground-state absorption to near-infrared (NIR) in tandem is a viable approach to identifying promising agents for these applications.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Rutênio/farmacologia , Absorção Fisico-Química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Teoria Quântica , Rutênio/química , Relação Estrutura-Atividade
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