Conjugated Pt(II) Complexes as Luminescence-Switch-On Reporters Addressing the Microenvironment of Bacterial Biofilms

Abstract

In this work, the synthesis, structural and photophysical characterization of six phosphorescent H 2 O-soluble Pt(II) complexes are reported while addressing their emission maxima, photoluminescence quantum yields (Φ L ), lifetimes (τ), aggregation tendency, and microenvironment sensitivity as a function of the substitution pattern on the main tridentate luminophore. Different ancillary ligands, namely, a trisulfonated phosphane and maltohexaose-conjugated pyridines (with or without amide bridges), were introduced and evaluated for the realization of switch-on-photoluminescent labels reporting on the microenvironment sensed in biofilms of Gram + and Gram − models, namely, Staphylococcus aureus and Escherichia coli. With the aid of confocal luminescence micro(spectro)scopy, we observed that selected complexes specifically interact with the biofilms while leaving planktonic cells unlabeled. By using photoluminescence lifetime imaging microscopy, excited-state lifetimes within S. aureus biofilms were measured. The photoluminescence intensities were drastically boosted, and the excited state lifetimes were significantly prolonged upon binding to the viscous biofilm matrix, mainly due to the suppression of radiationless deactivation pathways upon shielding from physical quenching processes, such as interactions with solvent molecules and 3 O 2 . The best performances were attained for non-aggregating complexes with maltohexaose targeting units and without amide bridges. Notably, in the absence of the maltodextrin, a hydrophobic adamantyl moiety suffices to attain a sizeable labeling capacity. Moreover, photoluminescence studies showed that selected complexes can also effectively interact with E. coli biofilms, where the bacterial cells are able to partially uptake the maltodextrin-based agents. In summary, the herein introduced concepts enable the development of specific biofilm reporters providing spatial resolution as well as lifetime-and spectrum-based readouts. Considering that most theragnostic agents reported so far mainly address metabolically active bacteria at the surface of biofilms but without reaching cells deeply immersed in the matrix, a new platform with a clear structure-property correlation is provided for the early detection of such bacterial arrays.

Monoanionic C^N^N Luminophores and Monodentate C-Donor Co-Ligands for Phosphorescent Pt(II) Complexes: A Case Study Involving Their Photophysics and Cytotoxicity

“…, d –π*) character. The weaker bands between 300 and 500 nm can be assigned to transitions into singlet excited states described as an admixture of LC and MLCT characters, where the contribution of the metal-based orbitals becomes more dominant, as seen in previous reports on related complexes. ,,,, Moreover, the calculated UV–vis spectra (by means of TD-DFT) nicely agree with the experimental data and confirm these assignments ( vide infra ).…”

“…The development of Pt­(II)-based anticancer agents illustrates one of the greatest developments in the field of inorganic medicinal chemistry, especially after the first implementation of cisplatin in chemotherapy. , To date, while there is an extensive number of coordination compounds of different transition-metal cations including Re­(I), Cu­(II), Ru­(II), Os­(II), Pd­(II), Ir­(III), and Au­(III), among many others, − Pt­(II) continues to be one of the most popular choices for metal-based anticancer drugs, principally due to the relatively high cure rates of specific neoplastic diseases. , In addition to cancer therapy, luminescent Pt­(II) complexes have recently received significant attention due to their broad spectrum of applications, from organic light-emitting diodes (OLEDs) manufacture , to other fields, for example, as bioimaging agents, − in photodynamic therapy, in photocatalysis, and as optical sensors . Pt­(II) complexes have a clear tendency toward aggregation, a process that is favored by the square-planar geometry of the d 8 -configured metal center.…”

“…As a consequence, the aggregation of Pt­(II) complexes leads to a broader red-shifted absorption and emission originating from states with formal metal–metal to ligand–ligand charge-transfer configuration (MMLLCT, d z 2 – d z 2 –π*−π*). − If compared with the ground state, such aggregates can show an excimeric character to variable extents due to the partial depopulation of an antibonding σ-orbital (derived from the overlap of two d z 2 lobes) with the partial occupation of an intermolecular bonding orbital (π*−π*) derived from ligand-centered (LC) antibonding orbitals. Instead, for the monomeric species, the photoluminescence occurs mainly from metal-perturbed ligand-centered ( 3 ML-LC) triplet states as admixtures of LC (π–π*) and metal-to-ligand charge transfer (MLCT, d –π*) character. ,, While the monomeric species can be quenched by diffusion-controlled processes such as a shortening of excited state lifetimes and/or reduction of emission intensity, the luminescence from aggregated species appears rather insensitive to 3 O 2 . Hence, they can be used in a variety of fields, such as ratiometric oxygen sensing, with aggregates as internal references, or in the field of bioimaging. , However, while for some applications, aggregation can be advantageous, it represents a drawback if color purity is desired, which is the case in electrophosphorescent devices such as OLEDs. , Additionally, both brightness and a defined composition are criteria to be fulfilled for biomedical applications. ,,− Since tailored Pt­(II) complexes can be used as biomarkers or in anti-cancer treatments, it is very important to control both photophysical and structural properties, such as emission color, lifetimes, and aggregation feasibility as they can affect their detection or interaction with biomembranes within the cellular environment or in the extra-cellular matrix as well as cellular uptake.…”

“…Instead, for the monomeric species, the photoluminescence occurs mainly from metal-perturbed ligand-centered ( 3 ML-LC) triplet states as admixtures of LC (π−π*) and metal-toligand charge transfer (MLCT, d−π*) character. 12,16,24 While the monomeric species can be quenched by diffusioncontrolled processes such as a shortening of excited state lifetimes and/or reduction of emission intensity, the luminescence from aggregated species appears rather insensitive to 3 as ratiometric oxygen sensing, with aggregates as internal references, or in the field of bioimaging. 16,21 However, while for some applications, aggregation can be advantageous, it represents a drawback if color purity is desired, which is the case in electrophosphorescent devices such as OLEDs.…”

Room-temperature luminescence from Pd(ii) and Pt(ii) complexes: from mechanochromic crystals to flexible polymer matrices

“…Luminescent transition metal complexes have been studied in the past years due to their broad range of applications including bioimaging, [1][2][3][4][5] photocatalysis, [6][7][8][9] OLEDs, [10][11][12] and optical sensors. [13][14][15][16][17][18] Among all the transition metals, Pt(II) complexes have been extensively explored, with more than 100 000 publications in the last 20 years, according to SciFinder © .…”