Platinum-containing drugs (e.g., cisplatin) are among the most frequently used chemotherapeutic agents. Their tremendous success has spurred research and development of other metal-based drugs, with notable achievements. Generally, the vast majority of metal-based drug candidates in clinical and developmental stages are stoichiometric agents, i.e., each metal complex reacts only once with their biological target. Additionally, many of these metal complexes are involved in side reactions, which not only reduce the effective amount of the drug but may also cause toxicity. On a separate note, transition metal complexes and nanoparticles have a well-established history of being potent catalysts for selective molecular transformations, with examples such as the Mo- and Ru-based catalysts for metathesis reactions (Nobel Prize in 2005) or palladium catalysts for C-C bond forming reactions such as Heck, Negishi, or Suzuki reactions (Nobel Prize in 2010). Also, notably, no direct biological equivalent of these transformations exists in a biological environment such as bacteria or mammalian cells. It is, therefore, only logical that recent interest has focused on developing transition-metal based catalytic systems that are capable of performing transformations inside cells, with the aim of inducing medicinally relevant cellular changes. Because unlike in stoichiometric reactions, a catalytically active compound may turn over many substrate molecules, only very small amounts of such a catalytic metallodrug are required to achieve a desired pharmacologic effect, and therefore, toxicity and side reactions are reduced. Furthermore, performing catalytic reactions in biological systems also opens the door for new methodologies to study the behavior of biomolecules in their natural state, e.g., via in situ labeling or by increasing/depleting their concentration at will. There is, of course, an art to the choice of catalysts and reactions which have to be compatible with biological conditions, namely an aqueous, oxygen-containing environment. In this review, we aim to describe new developments that bring together the far-distant worlds of transition-metal based catalysis and metal-based drugs, in what is termed "catalytic metallodrugs". Here we will focus on transformations that have been performed on small biomolecules (such as shifting equilibria like in the NAD/NADH or GSH/GSSG couples), on non-natural molecules such as dyes for imaging purposes, or on biomacromolecules such as proteins. Neither reactions involving release (e.g., CO) or transformation of small molecules (e.g., O production), degradation of biomolecules such as proteins, RNA or DNA nor light-induced medicinal chemistry (e.g., photodynamic therapy) are covered, even if metal complexes are centrally involved in those. In each section, we describe the (inorganic) chemistry involved, as well as selected examples of biological applications in the hope that this snapshot of a new but quickly developing field will indeed inspire novel research and unprecedented interactions across disciplinary boundaries.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrev.8b00493DOI Listing

Publication Analysis

Top Keywords

metal complexes
16
reactions
9
metal-based drugs
8
side reactions
8
reactions nobel
8
nobel prize
8
transition-metal based
8
biological
6
metal
5
intracellular catalysis
4

Similar Publications

Proteomic Profiling and Pre-Clinical Efficacy of Antimicrobial Lithium Complex and Colistin Combination against Multi-drug Resistant Acinetobacter baumannii.

Microb Pathog

January 2025

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan. Electronic address:

Multi-drug resistant (MDR) Acinetobacter baumannii accounts for high mortality rates in hospital-acquired infections. Colistin is the last resort treatment despite nephrotoxic effects and the emergence of colistin resistant A. baumannii.

View Article and Find Full Text PDF

Chemical associations of selenium oxyanions in metal oxides derived from layered double hydroxides: Implication for the immobilization of radionuclides.

Environ Res

January 2025

School of Creative Science and Engineering, Faculty of Science and Engineering, Waseda University, Tokyo 169-8050, Japan; Department of Earth Resources Engineering, Faculty of Engineering, Kyushu University, Fukuoka 819-0395, Japan. Electronic address:

Layered double hydroxides (LDHs) can effectively stabilize Se oxyanions, yet the thermal stability of Se oxyanions incorporated into LDHs remains unclear. In this study, calcination products of three types of LDHs loaded with SeO2- 3 or SeO2-4 were analyzed using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray absorption fine structure spectroscopy (XAFS) and leaching tests. It has been found that SeO2-4 can be reduced to SeO2- 3 in the Fe-containing LDHs after calcination at temperatures above 450 °C.

View Article and Find Full Text PDF

Pathogen invasion and persistent inflammatory storms caused by bacterial infections are the main challenges to the healing of infected wounds. Herein, this study proposed a pH-responsive polysaccharide hydrogel dressing (CG-HA) composed of cationic guar gum (CG) and hyaluronic acid (HA). Additionally, Zn and ferulic acid (FA)/β-cyclodextrin (β-CD) inclusion complexes (FA/β-CD) were co-introduced into the CG-HA hydrogel to form the desired FA/β-CD@CG-HA-Zn hydrogel.

View Article and Find Full Text PDF

Phases partitioning and occurrence forms of arsenic, chromium, and vanadium in a tidal reach of the Pearl River estuary, South China.

Environ Pollut

January 2025

Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, Chinese Academy of Sciences, Guangzhou 510650, China.

Migration characteristics and occurrence forms of redox-sensitive metal(loid)s such as arsenic (As), chromium (Cr), and vanadium (V) remained unclear in dynamic estuarine waters. In this work, size fractionation and chemical speciation of As, Cr, and V in the Jiaomen Waterway (JMW), a tidal river of the Pearl River estuary, were explored based on (ultra)filtration, the diffusive gradients in thin films (DGT) techniques and a thermodynamic chemical equilibrium model. The results showed that As was present mainly in soluble forms in the river water, and the suspended particulate matter (SPM) was identified the major carrier for Cr.

View Article and Find Full Text PDF

Predicting metal-binding proteins and structures through integration of evolutionary-scale and physics-based modeling.

J Mol Biol

January 2025

Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY, USA; Biology Department, Brookhaven National Laboratory, Upton, NY, USA. Electronic address:

Metals are essential elements in all living organisms, binding to approximately 50% of proteins. They serve to stabilize proteins, catalyze reactions, regulate activities, and fulfill various physiological and pathological functions. While there have been many advancements in determining the structures of protein-metal complexes, numerous metal-binding proteins still need to be identified through computational methods and validated through experiments.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!