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Cu(I) 4H-imidazolato complexes are excellent photosensitizers with broad and intense light absorption properties, based on an earth-abundant metal, and hold great promise as photosensitizers in artificial photosynthesis and for accumulation of redox equivalents. In this study, the excited-state relaxation dynamics of three novel heteroleptic Cu(I) 4H-imidazolato complexes with phenyl, tolyl, and mesityl side groups are systematically investigated by femtosecond and nanosecond time-resolved transient absorption spectroscopy and theoretical methods, complemented by steady-state absorption spectroscopy and (spectro)electrochemistry. After photoexcitation into the metal-to-ligand charge transfer (MLCT) and intraligand charge transfer absorption band, fast (0.6-1 ps) intersystem crossing occurs into the triplet MLCT manifold. The triplet-state population relaxes via the geometrical planarization of the N-aryl rings on the Cu(I) 4H-imidazolato complexes. Depending on the initial Franck-Condon state, the remaining small singlet state population relaxes into two geometrically distinct minima geometries with similar energy, S1/2,relax and S3/4,relax. Subsequent ground-state recovery from S1/2,relax and internal conversion from S3/4,relax to S1/2,relax take place on a 100 ps time scale. The internal conversion can be understood as hole transfer from a dyz-orbital to a dxz-orbital, which is accompanied with the structural reorganization of the coordination environment. Generally, the photophysical processes are determined by the steric hindrance of the side groups on the ligands. And the excited singlet-state pathways are dependent on the excitation wavelength.

We explore the photophysical properties of a family of Ru(II) complexes, Ru-ip-nT, designed as photosensitizers for photodynamic therapy (PDT). The complexes incorporate a 1H-imidazo[4,5-f][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, Ru-ip-3T (known as TLD1433), is currently in Phase II human clinical trials for treating bladder cancer by photodynamic therapy (PDT). The potent photocytotoxicity of Ru-ip-3T is attributed to a long-lived intraligand charge-transfer triplet state. The accessibility of this state changes upon varying the length (n) of the oligothiophene substituent. In this paper we highlight the impact of n on the ultrafast photoinduced dynamics in Ru-ip-nT, leading to the formation of the function-determining long-lived state. Femtosecond time-resolved transient absorption combined with resonance Raman data was used to map the excited-state relaxation processes from the Franck-Condon point of absorption to the formation of the lowest-energy triplet excited state, which is a triplet metal-to-ligand charge transfer ((3)MLCT) excited state for Ru-ip-0T-1T and an oligothienyl-localized triplet intraligand charge transfer ((3)ILCT) excited state for Ru-ip-2T-4T. We establish the structure-activity relationships with regard to changes in the excited state dynamics as a function of thiophene chain length, which alters the photophysics of the complexes and presumably impacts the photocytotoxicity of these photosensitizers.

TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to (3)ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for (1)O(2) generation and hence the potential of the complex to be used as a photocytotoxic agent. ENTRY FOR THE TABLE OF CONTENTS: A low-lying triplet intraligand state ((3)IL) determines the properties of the long-lived excited states in a series of Ru(II) complexes. The (3)IL state can be accessed by increasing the length of an oligothiophene chain. The (3)IL state is extremely efficient at generating (1)O(2) and thus enhances the potency of the complexes as PDT agents. [Image: see text]

Intracellular excited-state properties of a photodynamic active Osmium-complex are investigated. The key to the excited-state relaxation is the interplay of 3MLCT and 3ILCT states on the oligothiophene-substituted ligand. We successfully tested the model derived from solution with the complex internalized in cells to bridge the gap between cuvette and in vivo measurements for the first time. This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2(IP-4T)](PF6)2 with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug., publishedVersion

TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a Phase II study for treating non-muscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4′-dmb)(2)(IP-3T)]Cl(2) and TLD1633 = [Ru(4,4′-dmb)(2)(IP-4T)]Cl(2) (4,4′-dmb=4,4′-dimethyl-2,2′-bipyridine; 3T=α-terthiophene; 4T= α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest energy T(1) state is increased at the expense of a higher-lying triplet intraligand charge transfer ((3)ILCT) state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T(1) state. This lowest lying state is primarily responsible for O(2) sensitization and hence photoinduced cytotoxicity. Therefore, in order to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.

Cu(I) 4

A ruthenium complex with a half-sandwich geometry ([(p-cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated regarding its ultrafast photophysics. These photophysical investigations of the complex revealed a weak and short-lived emission from the initially populated 1MLCT state and solvent-dependent photoinduced dynamics, where the secondarily populated 3MC state is stabilized by nonpolar solvents. Overall the decay of the 3dd-MC state to the ground state is completed within picoseconds. This short excited-state lifetime is in stark contrast to the typically observed long-lived 3MLCT states with lifetimes of nanoseconds or microseconds in unstrained, octahedral ruthenium complexes but is in good agreement with the findings for distorted octahedral complexes. This is pointing to the half-sandwich geometry as a new and easy approach to study these otherwise often concealed dd states.

The excited state properties of three heteroleptic copper(I) xantphos 4H-imidazolate complexes are investigated by means of femtosecond and nanosecond time-resolved transient absorption spectroscopy in dichloromethane solution. The subpicosecond spectral changes observed after excitation into the MLCT absorption band are interpreted as intersystem crossing from the singlet to the triplet manifold. This interpretation is corroborated by DFT and TD-DFT results, indicating a comparable molecular geometry in the ground state (and hence the nonrelaxed singlet state) and the excited triplet state. Population of the triplet state is followed by planarization of the N-aryl rings of the 4H-imidazolate ligand on a 10 ps time scale. The planarization strongly depends on the substitution pattern of the N-aryls and correlates with the reduced moment of inertia for the planarization motion. The triplet state subsequently decays to the ground state in about 100 ns. These results demonstrate that the excited state processes of copper(I) complexes depend on the specific ligand(s) and their substitution pattern. Thus, the work presented points to a possibility to design copper(I) complexes with specific photophysical properties.

Eight difluoroboron complexes of curcumin derivatives carrying alkyne groups containing substituents have been synthesized following an optimised reaction pathway. The complexes were received in yields up to 98% and high purities. Their properties as fluorescent dyes have been investigated. Furthermore, a strategy for the hydrolysis of the BF2 group has been established using aqueous methanol and sodium hydroxide or triethylamine.

We present the synthesis and characterization of amphiphilic terpolymers containing photoacids based on 1-naphthol using reversible addition fragmentation chain transfer radical polymerization (RAFT). The respective poly(methyl methacrylate-co-2-(N,N-dimethylamino)ethyl methacrylate-co-1-naphthol methacrylate/methacrylamide) P[MMAx-co-DMAEMAy-co-NMAz/NMAmz] terpolymers were prepared starting from 1-naphthol derived monomers tNMA and tNMAm via RAFT polymerization und subsequent deprotection of the hydroxyl groups. The resulting materials were characterized using size exclusion chromatography and UV/Vis absorption spectroscopy, the latter also enabling the determination of pKa in the ground as well as the excited state of the monomers (NMA and NMAm). Afterwards, nanoprecipitation led to the formation of nanoparticles in aqueous media, which exhibited photo-responsive behavior upon UV-irradiation. Nile Red was encapsulated into the nanoparticles as a model hydrophobic guest molecule and we could demonstrate light-triggered release.

A ruthenium complex with a half-sandwich geometry ([(p-cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated regarding its ultrafast photophysics. These photophysical investigations of the complex revealed a weak and short-lived emission from the initially populated

Macrophages are the primary habitat of pathogenic mycobacteria during infections. Current research about the host-pathogen interaction on the cellular level is still going on. The present study proves the potential of Raman microspectroscopy as a label-free and non-invasive method to investigate intracellular mycobacteria in situ. Therefore, macrophages were infected with Mycobacterium gordonae, a mycobacterium known to cause inflammation linked to intracellular survival in macrophages. Here, we show that Raman maps provided spatial and spectral information about the position of bacteria within determined cell margins of macrophages in two-dimensional scans and in three-dimensional image stacks. Simultaneously, the relative intracellular concentration and distributions of cellular constituents such as DNA, proteins and lipids provided phenotypic information about the infected macrophages. Locations of bacteria outside or close to the outer membrane of the macrophages were notably different in their spectral pattern compared with intracellular once. Furthermore, accumulations of bacteria inside of macrophages exhibit distinct spectral/molecular information because of the chemical composition of the intracellular microenvironment. The data show that the connection of microscopically and chemically gained information provided by Raman microspectroscopy offers a new analytical way to detect and to characterize the mycobacterial infection of macrophages.

The class of cyclic lipopeptide natural products consists of compounds with a diverse range of bioactivities. In this study, we elucidated the structure of the cyclic lipopeptide anikasin using X-ray crystallography, analyzed its biosynthetic gene cluster, and investigated its natural role in the interaction between the producer strain Pseudomonas fluorescens HKI0770 and protozoal predators. These results led to the conclusion that anikasin has dual functionality enabling swarming motility and acting as a niche amoebicide, which effectively inhibits the social amoeba Polysphondylium violaceum and protects the producer strain from protozoal grazing.

In this study femtosecond and nanosecond time-resolved transient absorption spectroscopy was used to investigate the influence of ionic strength and complexity on the excited state dynamics of a Ru(II)-based metal–organic dyad. The bis-heteroleptic complex [Ru(bpy)2(ippy)]2+ (1), where bpy = 2,2′-bipyridine and ippy = 2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms owing to a long-lived triplet excited state derived from a metal-to-ligand charge-transfer (3MLCT) state that is equilibrium with an intraligand (3IL) state. The prolonged lifetime provides ample opportunity for bimolecular quenching of this state by oxygen; thus singlet oxygen (1O2) sensitization is very efficient. In simple aqueous solution, fast cooling within the 3MLCT manifold is followed by energy transfer to an 3IL state, which is facilitated by rotation of a pyrenyl unit about the imidazo–pyrenyl (ip) coannular b...