1. Introduction
The chemical industry is a cornerstone of modern society, supplying the materials and energy that drive human progress [
1]. Since the early 20th century, advances such as the large-scale syntheses of ammonia and phenolic resins, as well as the later manufacturing of pesticides, synthetic rubber, and antibiotics, have reshaped industrial production and everyday life. However, this progress has come at a cost—heavy energy and resource consumption, environmental pollution, and safety risks (
Fig. 1) [
2], [
3], [
4], [
5], [
6]. Emerging industries including artificial intelligence (AI), biotechnology, cell and gene therapy, precision medicine, photovoltaics, and batteries demand advanced materials with precisely controlled structures; they also have selectivity requirements for optical, electrical, magnetic, acoustic, and other functional properties. Against this backdrop, the future chemical industry faces three central challenges: ① reducing energy use and emissions to achieve a carbon peak and carbon neutrality, thereby enabling green, low-carbon growth; ② improving the intrinsic safety of chemical processes as a prerequisite for sustainable development; and ③ creating new, high-performance, multifunctional materials for emerging strategic sectors such as AI, renewable energy, and biotechnology (e.g., messenger ribonucleic acid (mRNA)/gene delivery), thus driving innovation and supporting high-quality socioeconomic development.
From a scientific perspective, new molecular products are generated via atomic-molecular reconstruction. The most critical scientific challenge lies in realizing the highly selective regulation of atomic-molecular reconstruction processes at industrial equipment scales. At their core, the three central challenges share a common scientific origin: an incomplete grasp of how flow and molecular mixing, interfacial transfer, and reaction/separation behave from the micro/nano scale down to the molecular scale [
7]. Classical chemical engineering focuses on the behavior of matter at the micro to macroscopic scales, where the flow, mass transfer, and reaction of bubbles, droplets, and particles are well described by the classical transport mechanisms of momentum, heat, and mass transfer, interacting alongside chemical reaction kinetics (together known in China as “three transfers and one reaction (3T + 1R)”), and have been successfully applied to scale-up and plant design. This framework, however, assumes the species within bubbles, droplets, and particles to be uniformly distributed below the nano/micro scale, whereas modern characterization shows the distribution to be non-uniform.
Molecular chemical engineering is the science and technology of chemical processes that enables precise and controllable chemical transformations (i.e., controllable molecular manufacturing) and physical processing at the molecular scale within industrial-scale process equipment (
Fig. 2) [
8], [
9], [
10], [
11]. In 2022, a research project entitled Chemical Process Intensification Toward the Nano/Micro Scale was approved by the National Natural Science Foundation of China. Relevant studies are being carried out through joint cooperation between researchers at Beijing University of Chemical Technology, Zhejiang University, and Xiamen University, focusing on solving the key scientific problems of how transport-reaction laws change at the molecular to nano/micro scales and how they interact to form synergistic mechanisms across scales. By using
in situ observation techniques for nano/micro fluid flow and process-intensification methods, researchers are constructing a cross-scale theoretical system to break through the knowledge gap and direct the cutting-edge discipline of molecular chemical engineering, offering a way to overcome the challenges of the conventional chemical industry and a path for the sustainable, high-quality development of the chemical industry.
2. Science of molecular chemical engineering
Chemical engineering science arose from industrial chemistry in the late 19th century to meet the need for large-scale production, and has since passed through three distinct stages. In the late 20th century, the industry’s rapid expansion and the rise of computing brought large-scale, strongly coupled, multi-variable system analysis to the field. Musun Guo at the Chinese Academy of Sciences proposed the “3T + 1R + X” paradigm of chemical engineering, where X stands for open, variable, and emerging elements [
12]. Since then, researchers in chemical engineering have increasingly focused on advancing technologies for characterizing mixing in chemical processes, understanding how multiscale reactor structures influence transport phenomena and reaction kinetics, and investigating structural evolution during reactor scale-up [
13], [
14]. Researchers have also come to realize that a new branch of engineering has emerged through the application of the theories and methods of molecular science and molecular engineering to fundamental chemical engineering problems. Combining molecular and atomic-scale design with computer-aided process design enables more effective industrial production and promotes advancements in chemical engineering [
15]. Therefore, chemical engineering is spearheading new developments from the macro scale down to the micro/nano and even molecular scales.
In 2009, the emergence of molecular chemical engineering was described as a shift in the discipline, driven by advances in computational methods and instrumentation, from macroscopic units (i.e., droplets, bubbles, and particles) to the molecular and atomic scales [
16]. It has also been widely recognized that, in order to eliminate the risk of failure in scale-up, stronger molecular-scale science is needed, including new theories of chemical reactions and of momentum, heat, and mass transfer spanning multiple scales [
17]. Leading institutions are now establishing the field of molecular chemical engineering in close collaboration with fellow engineering disciplines such as materials science, computer science, mechanical engineering, and environmental engineering, working in areas such as advanced materials, energy storage, and resource recycling. For example, Chen et al. [
13], [
14] began exploratory work on mixing and reaction engineering at the nano/micro scale in the late 1980s. Subsequent research found that micromixing at the nano/micro scale can be intensified by two to three orders of magnitude in a rotating packed bed (RPB) reactor (i.e., the so-called HiGee reactor), which has become a cutting-edge process-intensification technology. The intensification of transport mechanisms and reaction kinetics achieved by RPB reactors at the nano/micro and even molecular scales ensures precisely controllable material structures, the production of high-purity electronic chemicals, and the development of inherently safe continuous manufacturing [
11], [
18], [
19], [
20].
For example, the dehydrochlorination reaction of 1,1,2-trichloroethane forms three isomeric structures. Among them, vinylidene chloride (VDC) is used to prepare high-barrier poly(vinylidene chloride) (PVDC) film, which can effectively prevent oxygen and moisture from entering a package and keeps packaged food fresh for weeks. The intrinsic rate of the main reaction forming VDC is high, causing the apparent reaction rate to be limited by the molecular mixing of the reactants, whereas the molecular mixing efficiency has almost no effect on the rate of byproduct generation [
21]. Hence, the composition of the reaction product can be regulated by modulating the molecular mixing. Using an RPB reactor for chemical process intensification toward the nano/micro scale significantly improves the rate ratio between the main and side reactions and reduces the formation of impurities (
Fig. 3(a)). Successful scale-up has been realized from the laboratory scale (1 t·a
−1), through the pilot scale (100 t·a
−1), to the industrial scale (30 000 t·a
−1).
In terms of improving inherent safety, nitrosyl sulfuric acid (NSA) is widely used as an important intermediate in diazotization in the fine-chemicals industry, while the conventional technology for production of NSA has low reaction efficiency and high energy consumption due to insufficient gas-liquid contact. In practice, with the same total production capacity of NSA, a single production line equipped with one HiGee reactor can successfully replace the original three lines with 12 conventional stirred-tank reactors (
Fig. 3(b)). Compared with the conventional process, the volume of the reactor can be reduced by one order of magnitude, with a remarkable 69% reduction in the quantity of equipment, 100% reduction in steam consumption, and 43% reduction in electricity consumption [
22].
In the field of molecular separation, the combination of electrostatic-field regulation within the separation medium and nano-confined spaces has led to the development of molecular-recognition-based separation methods and platform technologies that can overcome the challenges of separating and upgrading complex, structurally similar bio-based feedstocks, enabling the production of a series of important pharmaceutical and chemical products [
23]. The industrial applications of these emerging technologies verify that the concept of molecular chemical engineering provides important theoretical guidance for addressing key issues in chemical conversion, separation, and purification.
Recently, the convergence of physics, chemistry, and information science has given the field powerful new tools for observation and computation. With the advancement of super-resolution experimental testing techniques,
in situ liquid-cell transmission electron microscopy can be used to experimentally observe dynamic changes in the nano/micro structure of liquid-solid, gas-liquid, and gas-solid interfaces and nano-fluid flow [
24]. Moreover, spatiotemporally tracking the charge-transfer process can establish an experimental paradigm for revealing the complex mechanisms of chemical reactions at the molecular and atomic level [
25]. These techniques make it possible to observe molecular transport and reaction at the nano/micro scale as they happen. For instance, at the molecular scale, a key property such as the molecular diffusion coefficient would no longer be merely a function of temperature and pressure but could also be significantly influenced by molecular-scale manipulation. A typical example is Knudsen diffusion: When a nanopore wall is present, the diffusion behavior shifts from ordinary molecular diffusion to Knudsen diffusion [
26]. Deeper insight into the patterns of these phenomena, such as molecular diffusion behavior under a high-gravity field and other local microenvironments, will facilitate the development of disruptive technologies in chemical engineering.
On the computational side, quantum chemistry and multiscale molecular simulation have advanced rapidly, promoted by faster hardware and by progress in algorithms and information technology, including high-performance and cloud computing, quantum computers, large databases, machine learning, and AI [
27], [
28], [
29]. These gains have extended both the accuracy and the temporal and spatial reach of simulations, making it possible to model complex multi-molecular systems from first principles and thereby simulate transport and reaction process at the nano/micro scale precisely, uncovering the mechanisms that govern them. Taken together, these examples of fundamental research, technological innovations, and industrial practices demonstrate that molecular chemical engineering is ushering in a new era spanning the molecular to industrial plant scales, promoting the high-quality development of the chemical industry.
3. Future prospects for molecular chemical engineering
Classical chemical engineering constitutes a systematic theoretical framework built upon an understanding of transport-mechanism and reaction rules at the macroscale (generally the micrometer scale and above, visible to the naked eye). Its scientific understanding and theoretical descriptions of flow, transport, and reaction processes at scales at and above bubbles, droplets, and particles (i.e., millimeter scale) are well-established and have been successfully applied to chemical process scale-up and plant engineering design. Nevertheless, the classical theory of chemical engineering is predicated on the hypothesis that the substances inside bubbles, droplets, and particles (i.e., the micro/nano scale) are homogeneously distributed, whereas advances in modern scientific characterization technologies have revealed that the substances within bubbles, droplets, and particles at the nano/micro scale are heterogeneously distributed. Research and industrial applications of process-intensification technologies, such as high-gravity engineering and microchemical engineering, have demonstrated that intensifying mass transport and mixing at the nano/micro scale can drastically raise the yield of fast-reaction industrial systems and substantially improve the structural controllability of advanced materials. This has established the new research paradigm and disciplinary system of molecular chemical engineering, centered on transport-reaction mechanisms from the molecular to nano/micro scales (
Fig. 4(a)). Accordingly, the fundamental scientific pathway to address the major challenges confronting the chemical industry and achieve the industry’s high-quality sustainable development involves the following undertakings: deeply uncovering the intrinsic microscale mechanisms of chemical engineering processes; bridging the knowledge gap in understanding flow, molecular mixing, interfacial transport, reaction, and separation rules spanning the micro/nano to molecular scales; and realizing the precise control of molecular-level chemical transformations and controllable molecular structures (i.e., atomic arrangements) of products at the industrial scale (
Fig. 4(b)).
Firstly, as the link between molecular behavior and bulk thermodynamic properties, molecular thermodynamics is moving from empirical correlation toward prediction and design at the molecular level. Theoretical work in this field centers on describing intermolecular interactions quantitatively and explaining phase behavior in complex fluids. Joining quantum-chemical calculation with statistical mechanics allows general models to connect molecular structure to thermodynamic properties. Methodologically, modeling driven by AI and large datasets is becoming important, with machine learning being used to find hidden patterns in experimental and simulated data and to build methods that are both accurate and physically interpretable. Combined with multiscale simulation and in situ characterization, these efforts supply the theoretical and quantitative tools required to solve problems such as designing energy-storage materials and drug-delivery systems. They also help shift chemical engineering from a focus on macroscopic process optimization toward the precise regulation of molecular functions.
At the nano/micro scale, fluids behave in markedly non-ideal ways that are not readily explained by classical theory. The questions of how nano/micro structures form at liquid-solid, gas-solid, and solid-solid interfaces and how electrons and molecules transfer across these interfaces are a bottleneck in the development of high-performance materials, while knowledge of how species diffuse and how diffusion couples with reactions within nano-confined channels is central to achieving catalytic and separation efficiency. These behaviors remain poorly understood and call for systematic, quantitative description. An integrated platform for the in situ characterization of nano/micro scale fluids, used alongside multiscale simulation and first-principles calculation, would make it possible to grasp the common principles governing flow, mixing, transport, and reaction at this scale and to track how they evolve within molecular and nanoclusters, at phase interfaces, and in confined spaces, providing the scientific basis for a theory of process intensification at the nano/micro scale. The transformation of matter and the making of new substances are based on the collision, splitting, and rearrangement of molecules, atoms, and ions. Because of a lack of understanding of the transport and reaction of molecules and their aggregates at the nano/micro scale, how they evolve, and how they can be controlled, scale-ups often encounter difficulties or risks: With changes in mass, heat, and/or momentum transport, the macro and micro environments around the reaction molecules change, the selectivity and yield fall, and undesired chemicals and microstructures are produced that affect the product performance and value, as well as the process energy and material consumption. What is needed is a clear understanding of how intensified transport and reaction act together at this scale, the means to design and build molecular and nanostructures deliberately, transport-reaction models spanning the molecular to the nano/micro scales, and new process-intensification technologies based on this knowledge and technology. The aim is to synthesize advanced materials and products with defined function and structure while reducing energy and raw-material consumption and improving intrinsic safety across material synthesis and high-end manufacturing.
4. Conclusions
Molecular chemical engineering involves the scale extension of chemical engineering from the macroscale to the micro/nano scale and ultimately to the molecular scale. It well conforms to the underlying pattern governing the evolution of chemical engineering, which has progressively advanced from macroscopy to microscopy and from phenomenological description to essential mechanism revelation. As the continuation and in-depth development of this evolutionary trend in the 21st century, molecular chemical engineering is an inevitable and transformative choice for the disciplinary advancement of chemical engineering. The rapid development of science and technology has laid a solid foundation for research in molecular chemical engineering. In particular, the interdisciplinary integration of physics, chemistry, information science, and other disciplines delivers powerful tools for dynamic in situ experimental observation, as well as theoretical simulation and computation spanning the molecular to nano/micro scales, making it feasible to address the challenge of precise calculation for chemical engineering processes in large-scale complex systems. The breakthrough of molecular chemical engineering necessitates profound interdisciplinary integration among the disciplines of chemical engineering, chemistry, materials science, information technology, and so on. Looking forward, by developing novel systems for optimizing the design of reaction and separation processes that integrate molecular chemical engineering theories, chemical engineers will play critical roles in accelerating the translation of novel chemicals and advanced materials into practical manufacturing and commercial applications for human being’s better life.
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