Modern chemical synthesis has reached the molecular level, that is, a small amount of atoms or molecules can be used to assemble supermacromolecules and microstructures, instead of traditional chemical synthesis in test tubes using large doses of substances to provide a whole environment (high temperature and high pressure catalysts, etc.). However, at the level of chemical self-assembly, the thermal motion of atoms and molecules is very violent. The synthesis of molecules has chemical structure and physical structure, so many problems are urgently solved. Let’s popularize this problem below:
Figure 1 From building block assembly to 3D printing to molecular self-assembly (delete infringement)
18. How far can we go on the road of chemical self-assembly? How Far Can We Push Chemical Self-Asembly? https://www.science.org/doi/10.1126/science.309.5731.95
Now most people already know that matter is made up of very small atoms. However, most physicists are not very concerned about how these matters are made, but about what laws of motion and secrets of change are behind the nature composed of various matters. They also prefer to study the complex laws of movement and change that dominate the complex matter in nature. However, chemists are different. Chemists like creation and are obsessed with revealing how various substances in nature were created by God. In professional terms, they like synthesis.
From the perspective of modern discipline classification, at least there is no so-called synthetic astronomy or synthetic physics yet, so chemistry and physics have always been two completely different research fields. Of course, physicists also need to make things and samples for experiments, but most of them are assembled at the macro level. They often use physical methods of mechanical cutting, and at most heat and melt forging, that is, top-down methods from the macro scale to the micro scale. Chemists are more concerned about how to "cut and synthesize" new molecules or new substances from the microscopic level, that is, from the bottom to the top method from the microscopic scale to the macroscopic, and their method is called chemical methods. So chemists have always tried every means to find new technologies and methods in molecular synthesis.
Figure 2 Two different methods of physics and chemistry (from the Internet infringement)
More than 100 years have passed since " alchemy " started. Chemists have been obsessed with using chemical methods such as heating, pressurization and catalyst addition to break the covalent bond of molecules, successfully causing the covalent bond formed by sharing electrons between atoms to break and cause other atoms to bind to form new covalent bonds, thereby synthesizing different molecules. Using this chemistry synthesis method, chemists have learned to freely combine up to 1,000 atoms into any molecular structure they like.
Although the synthesis methods of high-energy molecules mastered by chemists have left a deep impression on people, compared with the nature that is full of various complex forms of matter around us, the synthesis of chemists at the molecular level is simply not worth mentioning in front of nature. In nature, all matter forms, from small cells to cedar trees, are composed of countless small molecules connected together through weak interactions. These weak interactions, such as hydrogen bond , van der Waals force , and π-π interaction, control the assembly and formation of all material forms, including the double helix structure of DNA molecules, the synthesis of proteins (as shown in Figure 3) to the combination of water molecules to form liquid water. This subtle force that exists between molecules can not only drive the molecular movement, but also enable the molecules to gather together spontaneously and assemble into more complex structures.
Figure 3 The process of assembling hemoglobin through amino acids in human cells (pictures are from the Internet infringement)
phospholipid molecules will self-assemble and bind to form cell membranes, cells will self-assemble and bind to form tissues and organs, and tissues and organs will automatically assemble and form the entire organism.But to this day, chemists' chemical synthesis ability remains at the molecular level and is far from reaching the conventional level close to the creation of nature. Even those seemingly ordinary substances such as cell membranes in nature cannot be artificially controlled and easily synthesized. So chemists have successfully synthesized thousands of different inorganic and organic matter in the laboratory. Don’t they plan to use this ordinary self-assembly method in nature to synthesize more complex material structures above the molecular level?
In fact, don’t worry, they have already started this work. Over the past 30 years, chemists have made significant progress in understanding the basic rules of non-covalent bond synthesis. For example, one of these rules is: Birds of a feather flock together. Similar molecules prefer similar molecules, that is, molecular structures with similar properties tend to gather together, which we can see in the interaction between hydrophobic and hydrophilic. The hydrophilic and hydrophobic interaction between lipid molecules prompts the heads and tails of lipid molecules in water to gather together to form a two-layer membrane structure, thereby forming a protective layer surrounding the cells. The hydrophobic tails of the phospholipid molecules will spontaneously gather together to avoid any contact with water, while their polar hydrophilic heads gather together and all face the liquid (as shown in Figure 4). Another rule is that self-assembly is controlled by more energy-saving reactions. Excluding those molecules' inappropriate structures, the molecules will assemble them by themselves through appropriate low-energy input reactions to form complex and ordered structures.
Figure 4 Phospholipid molecular structure and self-assembled molecular membrane (picture from the Internet to delete)
Now chemists have learned to use these rules to design self-assembly systems with moderate complexity. For example, liposome that can carry drugs, this molecular system consists of a phospholipid bilayer similar to the cell membrane, and is commercially used to transport drugs to cancerous tissues in patients. Another molecule formed using self-assembly is called rotaxanes, which can oscillate back and forth between two stable states (as shown in Figure 5), and is expected to be made into molecular switches in the future and be applied to the core components of future molecular biological computers.
Figure 5 Rotaxanes and two different states (pictures from the Internet infringement)
However, due to the continuous development of computer circuit miniaturization and nano-micromachining technology, people's demand for complexity is growing. As computer chip processing sizes continue to shrink, the cost of manufacturing these increasingly small components is soaring. Nowadays, the method commonly adopted by chip manufacturing companies is still to create structures by physically reducing the material to the desired size, such as the physical method of photolithography or electron beam etching for microfabrication (as shown in Figure 6). However, to some extent, designing and manufacturing complex microstructures with a bottom-to-up approach by chemistry can make microprocessing processes more economical and cheap.
Figure 6 Computer's top-down lithography process (from the network infringement)
At the same time, self-assembly technology is also the only practical method to build various nanocomplex structures. However, it is not easy to ensure that the molecular components are assembled correctly. Because the force of intermolecular self-assembly self-assembly is very weak, self-assembly molecules may be constrained in an unwanted energy conformation, resulting in unavoidable defects in the assembly process. Therefore, any system that relies on self-assembly must be able to tolerate the existence of these defects, or be able to effectively repair these defects caused by self-assembly. To solve this problem, organisms once again provide us with very good examples in DNA assembly. When cells assemble the DNA molecule , enzymes will help replicate DNA strands during the cell division of , but they will always have errors in replication. For example, they occasionally insert A bases where T bases should be inserted. Some of these errors are not discovered, but most are captured by DNA repair enzymes that rescan the newly synthesized DNA strands and promptly correct errors in replication.
Figure 5 DNA assembly process in human cells (infringement and delete)
But strategies like DNA replication in are not easy for chemists to follow. But if they want to build complex and ordered system structures from the molecular level from the bottom up, they must be accustomed to thinking about some issues of molecular assembly in natural ways. However, whether we can use molecular self-assembly technology to create reliable chips, or create nanorobot that can work stably and safely in vascular tissue, or produce active cells or even biological tissue , which still requires continuous trial and exploration by chemists. Although this road is difficult, it is also full of fascinating opportunities and challenges. (Text Robert F. Servic)
