Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems

It is challenging to design metal catalysts for in situ transformation of endogenous biomolecules with good performance inside living cells. Herein, we report a multifunctional metal catalyst, ruthenium‐coordinated oligo(p‐phenylenevinylene) (OPV‐Ru), for intracellular catalysis of transfer hydrogenation of nicotinamide adenine dinucleotide (NAD+) to its reduced format (NADH). Owing to its amphiphilic characteristic, OPV‐Ru possesses good self‐assembly capability in water to form nanoparticles through hydrophobic interaction and π–π stacking, and numerous positive charges on the surface of nanoparticles displayed a strong electrostatic interaction with negatively charged substrate molecules, creating a local microenvironment for enhancing the catalysis efficiency in comparison to dispersed catalytic center molecule (TOF value was enhanced by about 15 fold). OPV‐Ru could selectively accumulate in the mitochondria of living cells. Benefiting from its inherent fluorescence, the dynamic distribution in cells and uptake behavior of OPV‐Ru could be visualized under fluorescence microscopy. This work represents the first demonstration of a multifunctional organometallic complex catalyzing natural hydrogenation transformation in specific subcellular compartments of living cells with excellent performance, fluorescent imaging ability, specific mitochondria targeting and good chemoselectivity with high catalysis efficiency.

Section: Figurementioning

confidence: 99%

Fluorescent and Biocompatible Ruthenium‐Coordinated Oligo(p‐phenylenevinylene) Nanocatalysts for Transfer Hydrogenation in the Mitochondria of Living Cells

Dai

Zhao

et al. 2020

“…[26,27] The transfer hydrogenationw as further exploited in vivo with iridium complexes acting as reduction catalysts for the removal of xenobiotic aldehydes from mammalian cell lines using NADH as the terminal reductant. [28,29] Additionally,a no xidase-like activityo fi ridium metallacycles was discovered in which NADH is driving the generation of hydrogen peroxidef rom dioxygen. [30] The metalcatalyzed interaction between dihydrogen and nicotinamides, however, remained challenging and only recently the first effective systemsa ppeared in the literature (Scheme 5).…”

Section: Metal-mediated H 2 Productiont Hrough Cofactor Dehydrogenationmentioning

confidence: 99%

Chemoenzymatic Hydrogen Production from Methanol through the Interplay of Metal Complexes and Biocatalysts

Tavakoli

Armstrong

Naapuri

et al. 2019

Microbial methylotrophic organisms can serve as great inspiration in the development of biomimetic strategies for the dehydrogenative conversion of C1 molecules under ambient conditions. In this Concept article, a concise personal perspective on the recent advancements in the field of biomimetic catalytic models for methanol and formaldehyde conversion, in the presence and absence of enzymes and co‐factors, towards the formation of hydrogen under ambient conditions is given. In particular, formaldehyde dehydrogenase mimics have been introduced in stand‐alone C1‐interconversion networks. Recently, coupled systems with alcohol oxidase and dehydrogenase enzymes have been also developed for in situ formation and decomposition of formaldehyde and/or reduced/oxidized nicotinamide adenine dinucleotide (NADH/ NAD+). Although C1 molecules are already used in many industries for hydrogen production, these conceptual bioinspired low‐temperature energy conversion processes may lead one day to more efficient energy storage systems enabling renewable and sustainable hydrogen generation for hydrogen fuel cells under ambient conditions using C1 molecules as fuels for mobile and miniaturized energy storage solutions in which harsh conditions like those in industrial plants are not applicable.

“…[2,3] Although these approaches have been traditionally considered to be incompatible, small-molecule catalysts that can interface with cellular metabolism have the potentialt oe xpand biological function without the need for genetic manipulation. [4][5][6] For example,s uch biocompatible catalysts could be parto fc ellular factories,i nw hich they perform new-to-nature transformations to diversify molecules producedby an organism. [7][8][9][10] Thus, such ac oncertede ffort of synthetic chemistry and metabolic engineering could pave the way toward the direct synthesis of value-added compounds in cellular settings.A dditionally,b iocompatible catalysis holds promise for biomedical applications, such as targeted drug release/synthesis, [11][12][13][14][15] the disruption of cell-cellc ommunication or rescuing dysfunctional enzymes involvedi nh uman diseases.…”

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confidence: 99%

“…Moreover,m etabolite concentrationsa re typicallyl ow (< 1mm), compared to the standard substrate concentrationse mployed in organic synthesis. [5,6,16] Conversely, the complex intra and extracellular environments of organisms contain am yriado fc ompounds that can poison exogenously supplied catalysts or reagents. [17] Consequently, the discovery and optimization of biocompatible catalysts and reactions remain challenging.…”

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confidence: 99%

“…To evaluatet he feasibility of the proposed screening platform, we identified the uncaging of allyloxycarbonyl( alloc)protected amines as am odel reactionf rom the collection of bioorthogonal/biocompatible transformations reported in the literature. [6,30] Specifically, this transformation is often employed for the unmasking of prodrugs in vivo [13,31,32] and can readily be adapted to our proposed screening platform by alloc-protection of the amine functionality of an cAA ( Figure 1B). A number of differentc atalysts have been shown to catalyze this transformation with varying efficiencies.…”

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confidence: 99%

See 1 more Smart Citation

A Screening Platform to Identify and Tailor Biocompatible Small‐Molecule Catalysts

Rubini

Ivanov

Mayer

2019

Interfacing biocompatible, small‐molecule catalysis with cellular metabolism promises a straightforward introduction of new function into organisms without the need for genetic manipulation. However, identifying and optimizing synthetic catalysts that perform new‐to‐nature transformations under conditions that support life is a cumbersome task. To enable the rapid discovery and fine‐tuning of biocompatible catalysts, we describe a 96‐well screening platform that couples the activity of synthetic catalysts to yield non‐canonical amino acids from appropriate precursors with the subsequent incorporation of these nonstandard building blocks into GFP (quantifiable readout). Critically, this strategy does not only provide a common readout (fluorescence) for different reaction/catalyst combinations, but also informs on the organism's fitness, as stop codon suppression relies on all steps of the central dogma of molecular biology. To showcase our approach, we have applied it to the evaluation and optimization of transition‐metal‐catalyzed deprotection reactions.