Developing Roles for Phosphates Outside of Biology: A Systems Chemistry Approach Towards Abiotic Phosphate Fuels

Informazioni relative al progetto

PhosphotoSupraChem

ID dell’accordo di sovvenzione: 101117240

DOI

10.3030/101117240

Data della firma CE 15 Settembre 2023

Data di avvio 1 Gennaio 2024

Data di completamento 31 Dicembre 2028

Finanziato da

• European Research Council (ERC)

Costo totale

€ 1 499 063,00

Contributo UE

€ 1 499 063,00

Coordinato da

ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
Germany

Periodic Reporting for period 1 - PhosphotoSupraChem (Developing Roles for Phosphates Outside of Biology: A Systems Chemistry Approach Towards Abiotic Phosphate Fuels)

Periodo di rendicontazione: 2024-01-01 al 2026-06-30

Sintesi del contesto e degli obiettivi generali del progetto

Chemical reactions typically proceed in a thermodynamically preferred manner. In living systems, however, chemistry operates far from equilibrium: energy-rich molecules are continuously consumed to drive otherwise unfavorable reactions, reorganize molecular structures, and regulate complex behavior in time. These energy-consuming processes are fundamental to biology, yet reproducing similar behavior in synthetic chemical systems remains a major challenge.

A key difficulty lies in translating biological strategies into simple, abiotic chemistry. In cells, energy transduction is tightly coupled to molecular recognition, catalysis, and structural organization. Artificial systems, by contrast, often rely on isolated reactions or static molecular designs, limiting their ability to display adaptive or time-dependent behavior.

This project addresses this challenge by exploring chemically fueled non-equilibrium systems based on phosphate chemistry. Phosphates play a central role in biology as energy carriers and regulatory elements, yet their potential as programmable fuels in abiotic systems remains largely unexplored. Here, the project focuses on aminoacyl phosphate compounds, which combine chemical activation with structural features capable of directing reactivity and self-assembly in water.

Specifically, the project aims to:
(i) design phosphate-based fuels whose molecular structure encodes both reactivity and organization;
(ii) understand how fuel-driven chemistry can select between competing reaction pathways and generate transient chemical states;
(iii) demonstrate how fuel consumption can lead to information transfer, oligomer formation, and higher-order organization;
(iv) explore how chemical “waste” generated during fuel use can actively regulate system behavior rather than acting as an inert by-product.
(v) searching the sequence space for peptide materials using phosphate fuels and microfluidics

By combining chemical synthesis, reactivity and supramolecular organization, the project operates at the interface of systems chemistry, non-equilibrium thermodynamics, and materials discovery. The results are expected to advance fundamental understanding of how complex chemical behavior can emerge from simple components, and to provide new conceptual tools for designing adaptive, time-dependent chemical systems.

Ultimately, this work contributes to a broader effort to rethink chemistry as a dynamic, fuel-driven process, opening new perspectives for responsive materials, transient functionality, and the chemical origins of biological-like organization.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the reporting period, the project made substantial progress towards its scientific objectives, establishing aminoacyl phosphate fuels as a versatile platform for programming non-equilibrium chemical systems. The work demonstrated that phosphate fuels are not only energy carriers but also molecular information carriers capable of directing chemical reactivity, supramolecular organization, and reaction network behaviour.

A major achievement was the development of structure-encoded phosphate fuels, demonstrating that the molecular architecture of the fuel determines selective acyl transfer, reaction pathways, and transient self-assembly. We showed that subtle structural modifications of phosphate fuels regulate molecular recognition and chemical selectivity, allowing chemically fuelled systems to selectively recruit substrates and produce distinct reaction outcomes under identical conditions.

Another important milestone was the establishment of fuel reconfiguration as a new strategy for programming chemically fuelled reaction networks. By modifying phosphate fuels during system operation, we demonstrated that reaction pathways can be dynamically reprogrammed, allowing sequential access to different chemical states and expanding the accessible reaction space beyond conventional static fuel systems. This work has been published in Nature Communications, and a second study further extending this concept is currently under review in Nature Chemistry.

The project also made significant advances towards understanding how chemically fuelled systems transfer molecular information. Aminoacyl phosphate fuels were shown to direct selective peptide bond formation and to promote transient supramolecular organization, demonstrating how chemical information encoded within the fuel structure can be translated into covalent products and higher-order molecular organization. In parallel, the development of light-responsive phosphate fuels enabled external control over chemically fuelled reaction networks, providing temporal regulation of fuel activation and system behaviour.

One of the most significant breakthroughs of the project emerged from WP3, where phosphate-derived reaction products were found to actively regulate subsequent chemical transformations rather than acting as passive waste products. This discovery establishes a fundamentally new concept for chemically fuelled systems, in which reaction by-products participate in information transfer and generate secondary chemical responses. The first manuscript describing these waste-driven functions has been submitted to PNAS, while a second study is currently being prepared for submission to Science.

Overall, the work performed demonstrates that phosphate-based fuels provide a powerful and programmable platform for non-equilibrium chemistry, enabling selective acyl transfer, dynamic fuel reconfiguration, information transfer, and waste-driven regulation. These advances substantially extend the original objectives of the project and establish new design principles for adaptive chemical systems operating far from equilibrium.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The results of this project advance the state of the art in chemically fuelled and non-equilibrium chemistry by demonstrating that energy input, molecular structure, and pathway control can be integrated within a single class of abiotic chemical fuels. In many previously reported chemically fuelled systems, fuels primarily acted as energy sources, while reaction outcomes were determined by external catalysts or predefined reaction conditions. In contrast, this project demonstrates that the molecular structure of the fuel itself can encode reactivity, selectivity, molecular recognition, and dynamic behaviour.

A major advance beyond the state of the art is the demonstration of structure-encoded, pathway-selective chemistry in water. Rather than simply driving isolated reactions, the phosphate-based fuels developed in this project direct selective acyl transfer, transient self-assembly, and controlled reaction cascades, allowing competing reaction pathways to be programmed through fuel design. These findings establish a new strategy for controlling non-equilibrium reaction networks without enzymatic regulation.

Another important advance is the introduction of fuel reconfiguration as a new design principle for chemically fuelled systems. Instead of functioning as static energy carriers that are consumed during the reaction, phosphate fuels can be chemically reconfigured during system operation, enabling sequential reactivity, adaptive reaction pathways, and access to expanded chemical space. This substantially extends the functional scope of chemically fuelled reaction networks.

The project also establishes a new paradigm for the role of reaction by-products in non-equilibrium chemistry. Rather than acting as inert waste, phosphate-derived products were shown to actively regulate subsequent chemical transformations, enabling waste-driven chemical functions and secondary responses. This introduces an entirely new mechanism for information transfer and regulation in abiotic reaction networks and significantly broadens the conceptual framework of chemically fuelled systems.

Together, these advances transform chemically fuelled chemistry from a collection of isolated fuel-driven reactions into a programmable platform in which the fuel itself encodes molecular information, directs reaction pathways, and regulates system behaviour over time. The design principles established by this project provide a foundation for the development of adaptive chemical systems, responsive materials, and increasingly life-like abiotic reaction networks.