Combinatorial Synthesis toward the Discovery of Highly Cytotoxic Fe(III) Complexes DOI

Felix Niemeier,

Lisa-Marie Servos,

Zisis Papadopoulos

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Cancer remains one of the deadliest diseases worldwide, with some tumors proving difficult to treat and increasingly resistant current therapies. Capitalizing on this, there is a need for new therapeutic agents novel mechanisms action. Among promising candidates, Fe(III) complexes have gained significant attention as potential chemotherapeutic agents. However, research these compounds has been limited small number, leading inefficiencies in drug discovery. This study addresses limitations by developing combinatorial library 495 synthesized from aminophenol, hydroxybenzaldehyde, pyridine derivatives. The were screened cytotoxicity against human breast adenocarcinoma noncancerous fibroblasts, identifying class modest cancer cell selectivity. lead compound effectively eradicated tumor spheroids at low micromolar concentrations, highlighting this approach rapid

Language: Английский

Discovery of antibacterial manganese(i) tricarbonyl complexes through combinatorial chemistry DOI Creative Commons
Mirco Scaccaglia,

Michael P. Birbaumer,

Silvana Pinelli

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(11), P. 3907 - 3919

Published: Jan. 1, 2024

To accelerate the discovery of novel metalloantibiotics we applied combinatorial synthesis to preparation 420 manganese tricarbonyl complexes.

Language: Английский

Citations

12
Iridium(III) complexes as novel theranostic small molecules for medical diagnostics, precise imaging at a single cell level and targeted anticancer therapy DOI Creative Commons
Patryk Szymaszek, Małgorzata Tyszka‐Czochara, Joanna Ortyl

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116648 - 116648

Published: July 3, 2024

Medical applications of iridium (III) complexes include their use as state-of-the-art theranostic agents - molecules that combine therapeutic and diagnostic functions into a single entity. These offer promising avenue in medical diagnostics, precision imaging at single-cell resolution targeted anticancer therapy due to unique properties. In this review we report short summary application level therapy. The exceptional photophysical properties Iridium complexes, including brightness photostability, make them excellent candidates for bioimaging. They can be used image cellular processes the microenvironment within cells with unprecedented clarity, aiding understanding disease mechanisms molecular level. Moreover designed selectively target cancer cells,. Upon targeting, these act photosensitizers photodynamic (PDT), generating reactive oxygen species (ROS) upon light activation induce cell death. integration capabilities offers potential holistic approach treatment, enabling not only precise eradication but also real-time monitoring treatment efficacy progression. This aligns goals personalized medicine, offering hope more effective less invasive strategies.

Language: Английский

Citations

8
Leveraging the Photofunctions of Transition Metal Complexes for the Design of Innovative Phototherapeutics DOI Creative Commons
Lawrence Cho‐Cheung Lee, Kenneth Kam‐Wing Lo

Small Methods, Journal Year: 2024, Volume and Issue: 8(11)

Published: Sept. 25, 2024

Abstract Despite the advent of various medical interventions for cancer treatment, disease continues to pose a formidable global health challenge, necessitating development new therapeutic approaches more effective treatment outcomes. Photodynamic therapy (PDT), which utilizes light activate photosensitizer produce cytotoxic reactive oxygen species (ROS) eradicating cells, has emerged as promising approach due its high spatiotemporal precision and minimal invasiveness. However, widespread clinical use PDT faces several challenges, including inefficient production ROS in hypoxic tumor microenvironment, limited penetration depth biological tissues, inadequate accumulation photosensitizers at site. Over past decade, there been increasing interest utilization photofunctional transition metal complexes applications their intriguing photophysical photochemical properties. This review provides an overview current design strategies used innovative phototherapeutics, aiming address limitations associated with achieve The challenges future perspectives on translation are also discussed.

Language: Английский

Citations

6
Discovery of Phototoxic Metal Complexes with Antibacterial Properties via a Combinatorial Approach DOI Creative Commons
Timothy Kench,

N Chowdhury,

Khondaker Miraz Rahman

et al.

Inorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Antimicrobial resistance is one of the biggest global healthcare challenges. Therefore, there an urgent need to develop new molecules that display distinct antibacterial properties overcome resistance. With this aim, we have developed a combinatorial and semiautomated platform synthesize screen library 78 compounds against Gram-positive Gram-negative bacteria. This based on octahedral iridium(III) complexes with general formula [Ir(CN)2(NN)]Cl (where CN are cyclometallating polyaromatic ligands NN phenanthroline-imidazole or dipyridophenazine derivatives) which known generate reactive oxygen species (ROS) upon light irradiation. From initial entire (in dark under irradiation) Escherichia coli Staphylococcus aureus, show scaffold highly effective at inhibiting growth bacteria intermediate dose (16 μg/mL), displaying hit rate >30% in rising 56% Six were selected for further studies panel five strains, allowing us identify two lead MICs as low 2 μg/mL. These studied more detail establish their mode action using time-kill study S. aureus USA300 strain.

Language: Английский

Citations

0
Rationally Designed Ir(III) Complex with an Exceptionally Strong Binding to Human Serum Albumin for Targeted Photodynamic Therapy DOI
Antonio Linero-Artiaga,

Lisa-Marie Servos,

Venancio Rodrı́guez

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

The application of iridium(III) complexes in photodynamic therapy (PDT) is often limited by their poor selectivity for cancerous cells, necessitating high drug doses that increase the risk side effects. development efficient delivery systems such as albumin conjugation therefore crucial to enhance tumor-targeted photosensitizers. To date, vast majority metal exhibit weak moderate binding with human serum albumin, limiting feasibility this approach. overcome limitation, rational design through molecular docking and density functional theory calculations a novel Ir(III) complex strong albumin-binding photosensitizer described. herein reported compound has highest constant ever an iridium complex, it showed photocatalytically produce reactive oxygen species upon blue light irradiation. presented well structural derivatives could have potential therapy.

Language: Английский

Citations

0
Discovery of Spin-Crossover Materials with Equivariant Graph Neural Networks and Relevance-Based Classification DOI
Angel Albavera-Mata,

Pawan Prakash,

Jason B. Gibson

et al.

Journal of Chemical Theory and Computation, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Swift discovery of spin-crossover materials for their potential application in electronic and quantum devices requires techniques that enable efficient identification suitable candidates. To this end, we screened the Cambridge Structural Database to develop a specialized database 1439 computed spin-switching energies from density functional theory each material. The was used train an equivariant graph convolution neural network predict magnitude spin-conversion energy. A test mean absolute error 360 meV. For candidate identification, equipped system with relevance-based classifier. This approach leads nearly 4-fold improvement identifying systems interest as compared conventional high-throughput screening.

Language: Английский

Citations

0
Advancing super-resolution microscopy with metal complexes: functional imaging agents for nanoscale visualization DOI

Nur Aininie Yusoh,

Martin R. Gill, Xiaohe Tian

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review highlights recent advancements in the use of metal complexes as functional imaging agents for nanoscale via super-resolution microscopy.

Language: Английский

Citations

0
Advanced strategies in the design of Ir(III) biscyclometalated complexes for PDT DOI
Juan Sanz-Villafruela, Arancha Carbayo, Marta Martı́nez-Alonso

et al.

Coordination Chemistry Reviews, Journal Year: 2025, Volume and Issue: 534, P. 216572 - 216572

Published: March 14, 2025

Language: Английский

Citations

0
Using experimental data in computationally guided rational design of inorganic materials with machine learning DOI Creative Commons
Heather J. Kulik

Journal of materials research/Pratt's guide to venture capital sources, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Language: Английский

Citations

0
Exploring Excited‐State Intramolecular Proton‐Coupled Electron Transfer in Dinuclear Ir(III)‐Complex via Covalently Tagged Hydroquinone: Phototherapy Through Futile Redox Cycling DOI Creative Commons
Maniklal Shee,

Julia Schleisiek,

Nishith Maity

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

Anticipating intramolecular excited-state proton-coupled electron transfer (PCET) process within dinuclear Ir2-photocatalytic system via the covalent linkage is seminal, yet challenging. Indeed, development of various complexes also promising for studying integral photophysics and facilitating applications in catalysis or biology. Herein, this study reports [Ir2(bis{imidazo-phenanthrolin-2-yl}-hydroquinone)(ppy)4]2+ (12+) complex by leveraging both ligand-centered redox property H-bonding exploring dual proton-transfer assisted PCET process. The vital role covalently placed hydroquinone bridged ligand investigated as electron-proton (ET-PT) mediator validated from triplet spin density plot. Moreover, bimolecular photoinduced ET reaction studied acetonitrile/water medium, forging lowest energy charge separated (3CSPhen-Im) state 12+ with methyl viologen favorably concerted-PCET pathway. result indicates strong donor-acceptors coupling, which limits recombination enhances catalytic efficiency. To showcase potential application, bioinspired PCET-based photocatalytic platform phototherapeutics, indicating significant mitochondrial localization leading to programmed cell death (apoptosis) through futile cycling. consequences effective internalization (via energy-dependent endocytosis), better safety profile, higher antiproliferative activity compared Cisplatin, explored 3D tumor spheroids, anticipates it be a lead compound.

Language: Английский

Citations

2