Let's try. I don’t think that everything written below is completely true, and I could well have missed something, but the analysis of existing answers to similar questions and my own thoughts lined up like this:
Take a hydrogen atom: one proton and one electron in its orbit.
The radius of a hydrogen atom is just the radius of the orbit of its electron. In nature, it is equal to 53 picometers, that is, 53 × 10^-12 meters, but we want to increase it to 30 × 10^-2 meters - about 5 billion times.
The diameter of a proton (that is, our atomic nucleus) is 1.75×10^−15 m. If you increase it to the desired size, it will be 1×10^−5 meters in size, that is, one hundredth of a millimeter. It is indistinguishable to the naked eye.
Let's better increase the proton immediately to the size of a pea. The orbit of the electron will then be the radius of a football field.
The proton will be a region of positive charge. It consists of three quarks, which are about a thousand times smaller than it - we will definitely not see them. There is an opinion that if this hypothetical object is sprinkled with magnetic chips, it will gather around the center into a spherical cloud.
The electron will not be visible. No ball will fly around the atomic nucleus, the "orbit" of the electron is just a region, at different points of which the electron can be located with different probabilities. You can imagine this as a sphere with a diameter of a stadium around our pea. At random points inside this sphere, a negative electric charge appears and instantly disappears. Moreover, it does it so quickly that even at any single moment of time it makes no sense to talk about its specific location ... yes, it's incomprehensible. Simply put, it doesn't "look" at all.
It is interesting, by the way, that by increasing the atom to macroscopic dimensions, we hope to "see" it - that is, to detect the light reflected from it. In fact, ordinary-sized atoms do not reflect light; on an atomic scale, we are talking about interactions between electrons and photons. An electron can absorb a photon and move to the next energy level, it can emit a photon, and so on. With this system hypothetically enlarged to the size of a football field, too many assumptions would be needed to predict the behavior of this impossible structure: would a photon have the same effect on a giant atom? Is it necessary to "look" at it by bombarding it with special giant photons? Will it emit giant photons? All these questions are, strictly speaking, meaningless. I think, however, it is safe to say that the atom will not reflect light in the way that a metal ball would.
As you know, everything material in the Universe consists of atoms. An atom is the smallest unit of matter that carries its properties. In turn, the structure of an atom is made up of a magical trinity of microparticles: protons, neutrons and electrons.
Moreover, each of the microparticles is universal. That is, you cannot find two different protons, neutrons or electrons in the world. All of them are absolutely similar to each other. And the properties of the atom will depend only on the quantitative composition of these microparticles in the general structure of the atom.
For example, the structure of a hydrogen atom consists of one proton and one electron. Next in complexity, the helium atom is made up of two protons, two neutrons, and two electrons. A lithium atom is made up of three protons, four neutrons and three electrons, etc.
Structure of atoms (from left to right): hydrogen, helium, lithium
Atoms combine into molecules, and molecules combine into substances, minerals and organisms. The DNA molecule, which is the basis of all life, is a structure assembled from the same three magical building blocks of the universe as the stone lying on the road. Although this structure is much more complex.
Even more amazing facts are revealed when we try to take a closer look at the proportions and structure of the atomic system. It is known that an atom consists of a nucleus and electrons moving around it along a trajectory that describes a sphere. That is, it cannot even be called a movement in the usual sense of the word. The electron is rather located everywhere and immediately within this sphere, creating an electron cloud around the nucleus and forming an electromagnetic field.
Schematic representations of the structure of the atom
The nucleus of an atom consists of protons and neutrons, and almost the entire mass of the system is concentrated in it. But at the same time, the nucleus itself is so small that if you increase its radius to a scale of 1 cm, then the radius of the entire structure of the atom will reach hundreds of meters. Thus, everything that we perceive as dense matter consists of more than 99% of the energy connections between physical particles alone and less than 1% of the physical forms themselves.
But what are these physical forms? What are they made of, and how material are they? To answer these questions, let's take a closer look at the structures of protons, neutrons, and electrons. So, we descend one more step into the depths of the microcosm - to the level of subatomic particles.
What is an electron made of?
The smallest particle of an atom is an electron. An electron has mass but no volume. In the scientific view, the electron does not consist of anything, but is a structureless point.
An electron cannot be seen under a microscope. It is observed only in the form of an electron cloud, which looks like a fuzzy sphere around the atomic nucleus. At the same time, it is impossible to say with accuracy where the electron is located at a moment in time. Devices are capable of capturing not the particle itself, but only its energy trace. The essence of the electron is not embedded in the concept of matter. It is rather like an empty form that exists only in and through movement.
No structure has yet been found in the electron. It is the same point particle as the quantum of energy. In fact, an electron is energy, however, this is its more stable form than the one represented by photons of light.
At the moment, the electron is considered indivisible. This is understandable, because it is impossible to divide something that has no volume. However, there are already developments in the theory, according to which the composition of an electron contains a trinity of such quasiparticles as:
- Orbiton - contains information about the orbital position of the electron;
- Spinon - responsible for the spin or torque;
- Holon - carries information about the charge of an electron.
However, as we see, quasi-particles have absolutely nothing in common with matter, and carry only information.
Photographs of atoms of different substances in an electron microscope
Interestingly, an electron can absorb energy quanta, such as light or heat. In this case, the atom moves to a new energy level, and the boundaries of the electron cloud expand. It also happens that the energy absorbed by an electron is so great that it can jump out of the atomic system and continue its movement as an independent particle. At the same time, it behaves like a photon of light, that is, it seems to cease to be a particle and begins to exhibit the properties of a wave. This has been proven in an experiment.
Young's experiment
In the course of the experiment, a stream of electrons was directed onto a screen with two slits cut into it. Passing through these slits, the electrons collided with the surface of another projection screen, leaving their mark on it. As a result of this “bombardment” by electrons, an interference pattern appeared on the projection screen, similar to that which would appear if waves, but not particles, passed through two slits.
Such a pattern occurs due to the fact that the wave, passing between the two slots, is divided into two waves. As a result of further movement, the waves overlap each other, and in some areas they cancel each other out. As a result, we get many stripes on the projection screen, instead of one, as it would be if the electron behaved like a particle.
The structure of the nucleus of an atom: protons and neutrons
Protons and neutrons make up the nucleus of an atom. And despite the fact that in the total volume the core occupies less than 1%, it is in this structure that almost the entire mass of the system is concentrated. But at the expense of the structure of protons and neutrons, physicists are divided in opinion, and at the moment there are two theories at once.
- Theory #1 - Standard
The Standard Model says that protons and neutrons are made up of three quarks connected by a cloud of gluons. Quarks are point particles, just like quanta and electrons. And gluons are virtual particles that ensure the interaction of quarks. However, neither quarks nor gluons have been found in nature, so this model is subject to severe criticism.
- Theory #2 - Alternative
But according to the alternative unified field theory developed by Einstein, the proton, like the neutron, like any other particle of the physical world, is an electromagnetic field rotating at the speed of light.
Electromagnetic fields of man and the planet
What are the principles of the structure of the atom?
Everything in the world - subtle and dense, liquid, solid and gaseous - is just the energy states of countless fields that permeate the space of the Universe. The higher the energy level in the field, the thinner and less perceptible it is. The lower the energy level, the more stable and tangible it is. In the structure of the atom, as well as in the structure of any other unit of the Universe, lies the interaction of such fields - different in energy density. It turns out that matter is only an illusion of the mind.
Hydrogen atom capturing electron clouds. And although modern physicists can even determine the shape of a proton with the help of accelerators, the hydrogen atom, apparently, will remain the smallest object, the image of which makes sense to call a photograph. "Lenta.ru" presents an overview of modern methods of photographing the microworld.
Strictly speaking, there is almost no ordinary photography left these days. Images that we habitually call photographs and can be found, for example, in any Lenta.ru photo essay, are actually computer models. A light-sensitive matrix in a special device (traditionally it is still called a “camera”) determines the spatial distribution of light intensity in several different spectral ranges, the control electronics stores this data in digital form, and then another electronic circuit, based on this data, gives a command to the transistors in the liquid crystal display . Film, paper, special solutions for their processing - all this has become exotic. And if we remember the literal meaning of the word, then photography is “light painting”. So what to say that the scientists succeeded to photograph an atom, is possible only with a fair amount of conventionality.
More than half of all astronomical images have long been taken by infrared, ultraviolet and X-ray telescopes. Electron microscopes irradiate not with light, but with an electron beam, while atomic force microscopes scan the relief of the sample with a needle. There are X-ray microscopes and magnetic resonance imaging scanners. All these devices give us accurate images of various objects, and despite the fact that it is, of course, not necessary to speak of "light painting" here, we still allow ourselves to call such images photographs.
Experiments by physicists to determine the shape of a proton or the distribution of quarks inside particles will remain behind the scenes; our story will be limited to the scale of atoms.
Optics never get old
As it turned out in the second half of the 20th century, optical microscopes still have room to develop. A decisive moment in biological and medical research was the emergence of fluorescent dyes and methods that allow selective labeling of certain substances. It wasn't "just new paint", it was a real revolution.
Contrary to common misconception, fluorescence is not a glow in the dark at all (the latter is called luminescence). This is the phenomenon of the absorption of quanta of a certain energy (say, blue light) with the subsequent emission of other quanta of lower energy and, accordingly, a different light (when blue is absorbed, green will be emitted). If you put in a filter that allows only the quanta emitted by the dye to pass through and blocks the light that causes fluorescence, you can see a dark background with bright spots of dyes, and dyes, in turn, can color the sample extremely selectively.
For example, you can color the cytoskeleton of a nerve cell red, highlight the synapses in green, and highlight the nucleus in blue. You can make a fluorescent label that will allow you to detect protein receptors on the membrane or molecules synthesized by the cell under certain conditions. The method of immunohistochemical staining has revolutionized biological science. And when genetic engineers learned how to make transgenic animals with fluorescent proteins, this method experienced a rebirth: mice with neurons painted in different colors became a reality, for example.
In addition, engineers came up with (and practiced) a method of so-called confocal microscopy. Its essence lies in the fact that the microscope focuses on a very thin layer, and a special diaphragm cuts off the light created by objects outside this layer. Such a microscope can sequentially scan a sample from top to bottom and obtain a stack of images, which is a ready-made basis for a three-dimensional model.
The use of lasers and sophisticated optical beam control systems has made it possible to solve the problem of dye fading and drying of delicate biological samples under bright light: the laser beam scans the sample only when it is necessary for imaging. And in order not to waste time and effort on examining a large preparation through an eyepiece with a narrow field of view, the engineers proposed an automatic scanning system: you can put a glass with a sample on the object stage of a modern microscope, and the device will independently capture a large-scale panorama of the entire sample. At the same time, in the right places, he will focus, and then glue many frames together.
Some microscopes can accommodate live mice, rats, or at least small invertebrates. Others give a slight increase, but are combined with an X-ray machine. To eliminate vibration interference, many are mounted on special tables weighing several tons indoors with a carefully controlled microclimate. The cost of such systems exceeds the cost of other electron microscopes, and competitions for the most beautiful frame have long become a tradition. In addition, the improvement of optics continues: from the search for the best types of glass and the selection of optimal lens combinations, engineers have moved on to ways to focus light.
We have specifically listed a number of technical details in order to show that progress in biological research has long been associated with progress in other areas. If there were no computers capable of automatically counting the number of stained cells in several hundred photographs, supermicroscopes would be of little use. And without fluorescent dyes, all millions of cells would be indistinguishable from each other, so it would be almost impossible to follow the formation of new ones or the death of old ones.
In fact, the first microscope was a clamp with a spherical lens attached to it. An analogue of such a microscope can be a simple playing card with a hole made in it and a drop of water. According to some reports, such devices were used by gold miners in Kolyma already in the last century.
Beyond the diffraction limit
Optical microscopes have a fundamental drawback. The fact is that it is impossible to restore the shape of those objects that turned out to be much smaller than the wavelength from the shape of light waves: you can just as well try to examine the fine texture of the material with your hand in a thick welding glove.
The limitations created by diffraction have been partly overcome, and without violating the laws of physics. Two circumstances help optical microscopes dive under the diffraction barrier: the fact that during fluorescence quanta are emitted by individual dye molecules (which can be quite far apart from each other), and the fact that by superimposing light waves it is possible to obtain a bright spot with a diameter smaller than wavelength.
When superimposed on each other, light waves are able to cancel each other out, therefore, the illumination parameters of the sample are such that the smallest possible area falls into the bright region. In combination with mathematical algorithms that can, for example, remove ghosting, such directional lighting provides a dramatic improvement in image quality. It becomes possible, for example, to examine intracellular structures with an optical microscope and even (by combining the described method with confocal microscopy) to obtain their three-dimensional images.
Electron microscope before electronic instruments
In order to discover atoms and molecules, scientists did not have to look at them - molecular theory did not need to see the object. But microbiology became possible only after the invention of the microscope. Therefore, at first, microscopes were associated precisely with medicine and biology: physicists and chemists who studied much smaller objects managed by other means. When they also wanted to look at the microcosm, diffraction limitations became a serious problem, especially since the methods of fluorescence microscopy described above were still unknown. And there is little sense in increasing the resolution from 500 to 100 nanometers if the object to be considered is even less!
Knowing that electrons can behave both as a wave and as a particle, physicists from Germany created an electron lens in 1926. The idea underlying it was very simple and understandable to any schoolchild: since the electromagnetic field deflects electrons, it can be used to change the shape of the beam of these particles by pulling them apart, or, on the contrary, to reduce the diameter of the beam. Five years later, in 1931, Ernst Ruska and Max Knoll built the world's first electron microscope. In the device, the sample was first illuminated by an electron beam, and then the electron lens expanded the beam that passed through before it fell on a special luminescent screen. The first microscope only gave a magnification of 400 times, but the replacement of light with electrons paved the way for photographing with magnification hundreds of thousands of times: the designers had only to overcome a few technical obstacles.
The electron microscope made it possible to examine the structure of cells in a quality that was previously unattainable. But from this picture it is impossible to understand the age of the cells and the presence of certain proteins in them, and this information is very necessary for scientists.
Electron microscopes now allow close-up photographs of viruses. There are various modifications of devices that allow not only to shine through thin sections, but also to consider them in "reflected light" (in reflected electrons, of course). We will not talk in detail about all the options for microscopes, but we note that recently researchers have learned how to restore an image from a diffraction pattern.
Touch, not see
Another revolution came at the expense of a further departure from the principle of "illuminate and see." An atomic force microscope, as well as a scanning tunneling microscope, no longer shines on the surface of the samples. Instead, a particularly thin needle moves across the surface, which literally bounces even on bumps the size of a single atom.
Without going into the details of all such methods, we note the main thing: the needle of a tunneling microscope can not only be moved along the surface, but also used to rearrange atoms from place to place. This is how scientists create inscriptions, drawings and even cartoons in which a drawn boy plays with an atom. A real xenon atom dragged by the tip of a scanning tunneling microscope.
The tunneling microscope is called because it uses the effect of tunneling current flowing through the needle: electrons pass through the gap between the needle and the surface due to the tunneling effect predicted by quantum mechanics. This device requires a vacuum to operate.
The atomic force microscope (AFM) is much less demanding on environmental conditions - it can (with a number of limitations) work without air pumping. In a sense, the AFM is the nanotech successor to the gramophone. A needle mounted on a thin and flexible cantilever bracket ( cantilever and there is a “bracket”), moves along the surface without applying voltage to it and follows the relief of the sample in the same way as the gramophone needle follows along the grooves of a gramophone record. The bending of the cantilever causes the mirror fixed on it to deviate, the mirror deflects the laser beam, and this makes it possible to very accurately determine the shape of the sample under study. The main thing is to have a fairly accurate system for moving the needle, as well as a supply of needles that must be perfectly sharp. The radius of curvature at the tips of such needles may not exceed one nanometer.
AFM allows you to see individual atoms and molecules, but, like a tunneling microscope, it does not allow you to look under the surface of the sample. In other words, scientists have to choose between being able to see atoms and being able to study the entire object. However, even for optical microscopes, the insides of the studied samples are not always accessible, because minerals or metals usually transmit light poorly. In addition, there are still difficulties with photographing atoms - these objects appear as simple balls, the shape of electron clouds is not visible in such images.
Synchrotron radiation, which occurs during the deceleration of charged particles dispersed by accelerators, makes it possible to study the petrified remains of prehistoric animals. By rotating the sample under X-rays, we can get three-dimensional tomograms - this is how, for example, the brain was found inside the skull of fish that became extinct 300 million years ago. You can do without rotation if the registration of the transmitted radiation is by fixing the x-rays scattered due to diffraction.
And this is not all the possibilities that X-rays open up. When irradiated with it, many materials fluoresce, and the chemical composition of a substance can be determined by the nature of the fluorescence: in this way, scientists color ancient artifacts, the works of Archimedes erased in the Middle Ages, or the color of feathers of long-extinct birds.
Posing atoms
Against the backdrop of all the possibilities provided by X-ray or optical fluorescence methods, a new way of photographing individual atoms no longer seems like such a big breakthrough in science. The essence of the method that made it possible to obtain the images presented this week is as follows: electrons are plucked from ionized atoms and sent to a special detector. Each act of ionization strips an electron from a certain position and gives one point on the "photo". Having accumulated several thousand such points, the scientists formed a picture showing the most likely places for finding an electron around the nucleus of an atom, and this, by definition, is an electron cloud.
In conclusion, let's say that the ability to see individual atoms with their electron clouds is more like a cherry on the cake of modern microscopy. It was important for scientists to study the structure of materials, to study cells and crystals, and the development of technologies resulting from this made it possible to reach the hydrogen atom. Anything less is already the sphere of interest of specialists in elementary particle physics. And biologists, materials scientists and geologists still have room to improve microscopes even with a rather modest magnification compared to atoms. Experts in neurophysiology, for example, have long wanted to have a device that can see individual cells inside a living brain, and the creators of rovers would sell their souls for an electron microscope that would fit on board a spacecraft and could work on Mars.
An atom (from the Greek “indivisible”) is once the smallest particle of matter of microscopic dimensions, the smallest part of a chemical element that bears its properties. The constituents of the atom - protons, neutrons, electrons - no longer have these properties and form them together. Covalent atoms form molecules. Scientists study the features of the atom, and although they are already quite well studied, they do not miss the opportunity to find something new - in particular, in the field of creating new materials and new atoms (continuing the periodic table). 99.9% of the mass of an atom is in the nucleus.
Don't be intimidated by the title. The black hole, accidentally created by the staff of the National Accelerator Laboratory SLAC, turned out to be only one atom in size, so nothing threatens us. And the name "black hole" only remotely describes the phenomenon observed by researchers. We have repeatedly told you about the most powerful X-ray laser in the world, called
Trurl began to catch atoms, scraping electrons from them, kneading protons so that only his fingers flashed, prepared a proton dough, laid out electrons around it and - for the next atom; less than five minutes had passed before he held a bar of pure gold in his hands: he handed it to his muzzle, but she, having tasted the bar on her tooth and nodding her head, said:
- And indeed gold, but I can't chase atoms like that. I'm too big.
- Nothing, we'll give you a special apparatus! Trurl persuaded him.
Stanislav Lem, Cyberiad
Is it possible to see an atom with a microscope, to distinguish it from another atom, to follow the destruction or formation of a chemical bond, and to see how one molecule turns into another? Yes, if it is not a simple microscope, but an atomic force one. And you can and not be limited to observation. We live in a time when the atomic force microscope has ceased to be just a window into the microworld. Today, this instrument can be used to move atoms, break chemical bonds, study the stretch limit of single molecules - and even study the human genome.
Letters from xenon pixels
Considering atoms has not always been so easy. The history of the atomic force microscope began in 1979, when Gerd Karl Binnig and Heinrich Rohrer, working at the IBM Research Center in Zurich, began to create an instrument that would allow studying surfaces with atomic resolution. To come up with such a device, the researchers decided to use the tunnel transition effect - the ability of electrons to overcome seemingly impenetrable barriers. The idea was to determine the position of atoms in the sample by measuring the strength of the tunneling current that occurs between the scanning probe and the surface under study.
Binnig and Rohrer succeeded, and they went down in history as the inventors of the scanning tunneling microscope (STM), and in 1986 received the Nobel Prize in Physics. The scanning tunneling microscope has made a real revolution in physics and chemistry.
In 1990, Don Eigler and Erhard Schweitzer, working at the IBM Research Center in California, showed that STM could be used not only to observe atoms, but to manipulate them. Using the probe of a scanning tunneling microscope, they created perhaps the most popular image symbolizing the transition of chemists to working with individual atoms - they painted three letters on a nickel surface with 35 xenon atoms (Fig. 1).
Binnig did not rest on his laurels - in the year of receiving the Nobel Prize, together with Christopher Gerber and Calvin Quayt, who also worked at the IBM Zurich Research Center, he began work on another device for studying the microworld, devoid of the shortcomings that are inherent in STM. The fact is that with the help of a scanning tunneling microscope it was impossible to study dielectric surfaces, but only conductors and semiconductors, and in order to analyze the latter, a significant rarefaction had to be created between them and the microscope probe. Realizing that it was easier to create a new device than to upgrade an existing one, Binnig, Gerber, and Quait invented the atomic force microscope, or AFM. The principle of its operation is radically different: to obtain information about the surface, it is not the current strength that occurs between the microscope probe and the sample under study that is measured, but the value of the forces of attraction that arise between them, that is, weak non-chemical interactions - van der Waals forces.
The first working model of AFM was relatively simple. The researchers moved a diamond probe over the surface of the sample, connected to a flexible micromechanical sensor - a gold foil cantilever (attraction occurs between the probe and the atom, the cantilever bends depending on the force of attraction and deforms the piezoelectric). The degree of bending of the cantilever was determined using piezoelectric sensors - in a similar way, the grooves and ridges of a vinyl record are turned into an audio recording. The design of the atomic force microscope allowed it to detect attractive forces up to 10–18 newtons. A year after the creation of a working prototype, the researchers managed to obtain an image of the graphite surface topography with a resolution of 2.5 angstroms.
In the three decades that have passed since then, AFM has been used to study almost any chemical object - from the surface of a ceramic material to living cells and individual molecules, both in a static and dynamic state. Atomic force microscopy has become the workhorse of chemists and materials scientists, and the number of works in which this method is used is constantly growing (Fig. 2).
Over the years, researchers have chosen conditions for both contact and non-contact study of objects using atomic force microscopy. The contact method described above is based on the van der Waals interaction between the cantilever and the surface. When operating in a non-contact mode, the piezovibrator excites the probe oscillations at a certain frequency (most often resonant). The force acting from the surface leads to the fact that both the amplitude and the phase of the probe oscillations change. Despite some shortcomings of the non-contact method (first of all, sensitivity to external noise), it is precisely this method that excludes the effect of the probe on the object under study, and, therefore, is more interesting for chemists.
Alive on probes, chasing connections
Atomic force microscopy became non-contact in 1998 thanks to the work of Binnig's student, Franz Josef Gissible. It was he who suggested using a quartz reference oscillator of a stable frequency as a cantilever. After 11 years, researchers from the IBM laboratory in Zurich undertook another modification of the non-contact AFM: the role of the probe-sensor was performed not by a sharp diamond crystal, but by one molecule - carbon monoxide. This made it possible to move to subatomic resolution, as demonstrated by Leo Gross from the Zurich division of IBM. In 2009, with the help of AFM, he made visible not atoms, but chemical bonds, having obtained a fairly clear and unambiguously readable “picture” for the pentacene molecule (Fig. 3; Science, 2009, 325, 5944, 1110–1114, doi: 10.1126/science.1176210).
Convinced that a chemical bond could be seen with AFM, Leo Gross decided to go further and use the atomic force microscope to measure bond lengths and orders - key parameters for understanding the chemical structure, and hence the properties of substances.
Recall that the difference in bond orders indicates different electron densities and different interatomic distances between two atoms (in simple terms, a double bond is shorter than a single bond). In ethane, the carbon-carbon bond order is one, in ethylene it is two, and in the classic aromatic molecule, benzene, the carbon-carbon bond order is greater than one, but less than two, and is considered to be 1.5.
Determining the bond order is much more difficult when going from simple aromatic systems to planar or bulky polycondensed ring systems. Thus, the order of bonds in fullerenes consisting of condensed five- and six-membered carbon cycles can take any value from one to two. The same uncertainty theoretically applies to polycyclic aromatic compounds.
In 2012, Leo Gross, together with Fabian Mohn, showed that an atomic force microscope with a metal non-contact probe modified with carbon monoxide can measure differences in the distribution of charges among atoms and interatomic distances - that is, parameters associated with bond order ( Science, 2012, 337, 6100, 1326–1329, doi: 10.1126/science.1225621).
To do this, they studied two types of chemical bonds in fullerene - a carbon-carbon bond, common to two six-membered carbon-containing cycles of C 60 fullerene, and a carbon-carbon bond, common to five- and six-membered cycles. An atomic force microscope showed that the condensation of six-membered rings results in a bond that is shorter and of higher order than the condensation of C 6 and C 5 cyclic fragments. The study of the features of chemical bonding in hexabenzocoronene, where six more C6 cycles are symmetrically located around the central C 6 cycle, confirmed the results of quantum chemical modeling, according to which the order of C-C bonds of the central ring (in Fig. 4, the letter i) must be greater than the bonds that unite this ring with peripheral cycles (in Fig. 4, the letter j). Similar results were also obtained for a more complex polycyclic aromatic hydrocarbon containing nine six-membered rings.
The bond orders and interatomic distances, of course, were of interest to organic chemists, but it was more important for those who were engaged in the theory of chemical bonds, prediction of reactivity and the study of the mechanisms of chemical reactions. Nevertheless, both synthetic chemists and specialists in the study of the structure of natural compounds were in for a surprise: it turned out that the atomic force microscope can be used to establish the structure of molecules in the same way as NMR or IR spectroscopy. Moreover, it gives an unambiguous answer to questions that these methods are unable to cope with.
From photography to cinema
In 2010, the same Leo Gross and Rainer Ebel were able to unambiguously establish the structure of a natural compound - cephalandol A, isolated from a bacterium Dermacoccus abyssi(Nature Chemistry, 2010, 2, 821–825, doi: 10.1038/nchem.765). The composition of cephalandol A was previously determined using mass spectrometry, but analysis of the NMR spectra of this compound did not give an unambiguous answer to the question of its structure: four variants were possible. Using an atomic force microscope, the researchers immediately ruled out two of the four structures, and made the right choice of the remaining two by comparing the results obtained through AFM and quantum chemical modeling. The task turned out to be difficult: in contrast to pentacene, fullerene and coronenes, cephalandol A contains not only carbon and hydrogen atoms, in addition, this molecule has no symmetry plane (Fig. 5) - but this problem was also solved.
Further confirmation that the atomic force microscope could be used as an analytical tool came from the group of Oskar Kustanz, then at the Osaka University School of Engineering. He showed how, using AFM, to distinguish between atoms that differ from each other much less than carbon and hydrogen ( Nature, 2007, 446, 64–67, doi: 10.1038/nature05530). Kustanz investigated the surface of an alloy consisting of silicon, tin and lead with a known content of each element. As a result of numerous experiments, he found out that the force that arises between the tip of the AFM probe and different atoms differs (Fig. 6). For example, the strongest interaction was observed when probing silicon, and the weakest interaction was observed when probing lead.
It is assumed that in the future the results of atomic force microscopy for the recognition of individual atoms will be processed in the same way as the results of NMR - by comparison of relative values. Since the exact composition of the sensor needle is difficult to control, the absolute value of the force between the sensor and various surface atoms depends on the experimental conditions and the brand of the device, but the ratio of these forces for any composition and shape of the sensor remains constant for each chemical element.
In 2013, the first examples of using AFM to obtain images of individual molecules before and after chemical reactions appeared: a “photoset” is created from the products and intermediates of the reaction, which can then be mounted as a kind of documentary film ( Science, 2013, 340, 6139, 1434–1437; doi: 10.1126/science.1238187).
Felix Fisher and Michael Crommie of the University of California at Berkeley applied silver to the surface 1,2-bis[(2-ethynylphenyl)ethynyl]benzene, imaged the molecules and heated the surface to initiate cyclization. Half of the original molecules turned into polycyclic aromatic structures, consisting of fused five six-membered and two five-membered rings. Another quarter of the molecules formed structures consisting of four six-membered cycles linked through one four-membered cycle and two five-membered cycles (Fig. 7) . The remaining products were oligomeric structures and, in an insignificant amount, polycyclic isomers.
These results twice surprised the researchers. First, only two main products were formed during the reaction. Secondly, their structure caused surprise. Fisher notes that chemical intuition and experience made it possible to draw dozens of possible reaction products, but none of them corresponded to the compounds that formed on the surface. It is possible that the interaction of the initial substances with the substrate contributed to the occurrence of atypical chemical processes.
Naturally, after the first serious successes in the study of chemical bonds, some researchers decided to use AFM to observe weaker and less studied intermolecular interactions, in particular, hydrogen bonding. However, work in this area is just beginning, and their results are contradictory. So, in some publications it is reported that atomic force microscopy made it possible to observe the hydrogen bond ( Science, 2013, 342, 6158, 611–614, doi: 10.1126/science.1242603), in others they argue that these are just artifacts due to the design features of the device, and the experimental results should be interpreted more carefully ( Physical Review Letters, 2014, 113, 186102, doi:10.1103/PhysRevLett.113.186102). Perhaps the final answer to the question of whether it is possible to observe hydrogen and other intermolecular interactions using atomic force microscopy will be obtained already in this decade. To do this, it is necessary to increase the AFM resolution at least several times and learn how to obtain images without noise ( Physical Review B, 2014, 90, 085421, doi:10.1103/PhysRevB.90.085421).
Synthesis of one molecule
In skillful hands, both STM and AFM are transformed from instruments capable of studying matter into instruments capable of directionally changing the structure of matter. With the help of these devices, it has already been possible to obtain "the smallest chemical laboratories", in which a substrate is used instead of a flask, and individual molecules are used instead of moles or millimoles of reactants.
For example, in 2016, an international team of scientists led by Takashi Kumagai used non-contact atomic force microscopy to transfer the porphycene molecule from one of its forms to another ( Nature Chemistry, 2016, 8, 935–940, doi: 10.1038/nchem.2552). Porphycene can be considered as a modification of porphyrin, the inner cycle of which contains four nitrogen atoms and two hydrogen atoms. The vibrations of the AFM probe transferred enough energy to the porphycene molecule to transfer these hydrogens from one nitrogen atom to another, and as a result, a “mirror image” of this molecule was obtained (Fig. 8).
The group led by the indefatigable Leo Gross also showed that it was possible to initiate the reaction of a single molecule - they turned dibromoanthracene into a ten-membered cyclic diyne (Fig. 9; Nature Chemistry, 2015, 7, 623–628, doi: 10.1038/nchem.2300). Unlike Kumagai et al., they used a scanning tunneling microscope to activate the molecule, and the result of the reaction was monitored using an atomic force microscope.
The combined use of a scanning tunneling microscope and an atomic force microscope even made it possible to obtain a molecule that cannot be synthesized using classical techniques and methods ( Nature Nanotechnology, 2017, 12, 308–311, doi: 10.1038/nnano.2016.305). This triangulene is an unstable aromatic diradical, the existence of which was predicted six decades ago, but all attempts at synthesis were unsuccessful (Fig. 10). Chemists from the group of Niko Pavlicek obtained the desired compound by removing two hydrogen atoms from its precursor using STM and confirming the synthetic result using AFM.
It is assumed that the number of works devoted to the application of atomic force microscopy in organic chemistry will continue to grow. Currently, more and more scientists are trying to repeat on the surface of the reaction, well-known "solution chemistry". But perhaps synthetic chemists will begin to reproduce in solution those reactions that were originally carried out on the surface using AFM.
From non-living to living
Cantilevers and probes of atomic force microscopes can be used not only for analytical studies or the synthesis of exotic molecules, but also for solving applied problems. Cases of using AFM in medicine are already known, for example, for the early diagnosis of cancer, and here the pioneer is the same Christopher Gerber, who had a hand in developing the principle of atomic force microscopy and the creation of AFM.
Thus, Gerber managed to teach AFM to determine the point mutation of ribonucleic acid in melanoma (on the material obtained as a result of a biopsy). To do this, the gold cantilever of an atomic force microscope was modified with oligonucleotides that can enter into intermolecular interaction with RNA, and the strength of this interaction can still be measured due to the piezoelectric effect. The sensitivity of the AFM sensor is so high that it is already being used to study the effectiveness of the popular CRISPR-Cas9 genome editing method. It brings together technologies created by different generations of researchers.
Paraphrasing the classic of one of the political theories, we can say that we already see the limitless possibilities and inexhaustibility of atomic force microscopy and are hardly able to imagine what lies ahead in connection with the further development of these technologies. But even today, the scanning tunneling microscope and the atomic force microscope give us the opportunity to see atoms and touch them. We can say that this is not only an extension of our eyes, which allows us to look into the microcosm of atoms and molecules, but also new eyes, new fingers that can touch this microcosm and control it.