Indeed, oxygen is one of the most abundant chemical elements on the planet, and it has been baffling scientists since its official discovery in 1773 by Carl Wilhelm Scheele and Joseph Priestley, independently. You will know why I said official when we get to the some facts about oxygen later.

Associated with the chalcogen group, molecular oxygen, dioxygen, or O2, is an extremely volatile covalent compound.

As obvious as it may seem, the discovery of oxygen was key for the development of chemical science: In fact, the process of abstracting electrons from a molecule, known as the chemical process of oxidation, takes its name from this element. This is due to the fact that elemental oxygen has the capacity of forming “oxides” with most chemical elements.

Technically, it is also the third most abundant element in the universe, trailing behind hydrogen and helium, respectively. 

Hence, in this article, you will learn several facts about this fascinating chemical element. We want to get into its photochemical properties (i.e. its color). But also, you will hopefully discover new things to add up to your knowledge. Let’s get started. 

General Properties of Oxygen

First off, we will take a look into molecular oxygen’s physical and chemical properties.

Oxygen is a colorless and tasteless gas at normal circumstances. This chemical compound is virtually odorless. People have stated, however, that it is actually possible to distinguish between air or pure oxygen. If the odor of oxygen does exist, we may not smell it because of olfactory fatigue.

Os we already mentioned, the most common form of that the element oxygen takes is that of molecular oxygen, dioxygen, or simply O2.

Dioxygen molecules, which are found in gas form under standard conditions, are composed by two atoms of oxygen which are bound through a covalent bond to one another.

However, oxygen is not always in a gas form.

Like most chemical compounds, under certain conditions, which we are about to discuss, it can also transition to different states of matter.

Liquid Oxygen

Liquid oxygen is the condensed form of dioxygen. Nowadays, liquid oxygen is used in many industries such as submarine, and aerospace, or in medicine.

In 1877, liquid oxygen was first discovered by Louis Paul Cailletet (France) and Raoul Pictet (Switzerland). This was after Michael Faraday had liquefied most gases known by 1845, but failed to do so with 6 of them which were known as “permanent gases” at the time. Oxygen was one of those gases.

Slightly denser than water in a liquid state, liquid O2 has a density of precisely 1.141 g/cm3. At its freezing point of 54.36 K (−361.82 °F or −218.79 °C), it becomes a solid.

Furthermore, liquefied oxygen is paramagnetic, a special type of magnetism. Paramagnetic materials (such as liquid oxygen) become weakly attracted to an external magnetic field. Check out the experiment on this video:

Oxygen is also an oxidizing agent as it can readily oxidize organic or inorganic (such as metals) materials. It is in fact used as oxidizing agent in liquid-fueled rockets, since its invention in 1926 by Robert Goddard.

Solid Oxygen

Under standard atmospheric pressure, and at temperatures below 54.36 K (−361.82 °F, −218.79 °C), dioxygen transitions from gas to solid, forming a spin-lattice crystal. Also in this state, diatomic oxygen is one of the few small molecules that carry a magnetic dipole moment.

Color and Properties of Oxygen in Different States

Now the question is:

What is the color of oxygen? Well, gaseous oxygen is colorless. However, when in liquid form, it comes in a shade of pale sky-blue.

The color of solid oxygen, on the other hand, ranges from light blue, pink-to-faint blue, faint-blue, orange, dark-red-to-black, and metallic in six of its different possible phases.

You basically can have solid dioxygen in 6 different phases. And each of them display a particular color.

Why Is Liquid Oxygen Blue?

Similarly to what happens to water (which is also blue, by the way!), the energetic transitions of the electrons in oxygen (which are also the cause of its para magnetism) absorb light on the red spectrum. So red light is absorbed to some extent, giving the substance its complementary color: blue.

If you want more info, this paper in the Journal of Chemical Education gets you covered.

Other Facts About Oxygen

Oxygen is a fascinating chemical element. Apart from its physical and chemical properties, it also has a fascinating history. Add more to your new knowledge and digest some of the following facts below.

If you are hungry for even more, make sure to check our explanations to 100 chemistry facts!

Who Discovered Oxygen?

The question of “who” only brings confusion as sources may vary.

The earliest mention of oxygen is in Michael Sendivogius’s 1604 study. A Polish philosopher, physician, and alchemist, he motioned that air contains a substance called ‘cibus vitae,’ which translates as the food of life.

However, most scholars say that the real discoverer of oxygen is Carl Wilhelm Scheele, a Swedish pharmacist. Between the years 1771 and 72, Scheele experimented with various metal salts, including several nitrates. Scheele discovered the release of a then-unknown combustible agent.

Scheele wrote in his manuscript, Treatise on Air and Fire, his observations about a so-called ‘fire gas’ that is released from heating nitrates. He submitted his findings in 1775 and had them published two years later.

During that same time, though, Joseph Priestley, an aptly named British clergyman, observed that mercuric oxide in a glass tube released a gas he called ‘dephlogisticated air’ after sunlight exposure. He further noted that candles burned brighter in ‘dephlogisticated air’ and that a mouse lived longer even after being exposed to it. He also tried breathing it in and noted that it was like breathing regular air. Priestley published these findings in his 1775 paper called An Account of Further Discoveries in Air.

On a different note, Antoine Lavoisier, also made claims that he independently discovered this substance. Both Lavoisier and Priestley exchanged correspondence and shared ideas. However, the former denied having received any letter from Carl Wilhelm Scheele.

Where Did Oxygen Originate on Earth?

Oxygen comes in third as the most abundant element across the whole universe. However this only accounts for about 1% of oxygen, since the two main constituents, hydrogen and helium, account for 75% and 23% of the entire universe, respectively.

But it was relatively scarce during the formation of Earth.

Accordingly to theories, early forms of cyanobacteria have produced oxygen and added it into the atmosphere of our then-prehistoric planet. Like plants of today, these organisms used photosynthesis as a form of sustenance. For millions of years, they took in carbon dioxide and released oxygen — a grand event dubbed as the Great Oxidation Event.  

What Is the Effect of O2 in the Blood?

Oxygen is crucial to our bodily functions. Without it, we would not last long. Oxygen is not only the basic source of energy that fuels the activity of all cells in our body, but also has several other secondary functions such as serving as a buffering agent – keeping our pH levels in check.

The average blood O2 level is around 75-100 mm Hg or millimeters of mercury. When it drops below normal, we may experience shortness of breath. Likewise, our blood will become acidic because of an increase in blood carbon dioxide or CO2.

Now, what if blood O2 increases? We will experience hyperoxia, which, when aggravated, may lead to oxygen toxicity. This condition may also cause severe damage to your body.

Why Do We Turn Blue When Blood O2 Decreases?

Bright red is the color of oxygenated blood because of the protein, hemoglobin. However, when a person experiences hypoxia, hemoglobin will not bind with the red blood cells, resulting in a darker hue, making us appear as bluish.

Basically, oxygen forms a coordination complex with the ‘heme’ group on hemoglobin. This complex is red-colored, whereas free hemoglobin is actually blue.

Why Are Oxygen Atoms Usually Depicted in Red Color?

If you are familiar with molecular models (and you should!), for sure you know that oxygen atoms are usually red-colored.

Considering that these colors (CPK coloring system) are usually inspired by the color of the elements themselves (hydrogen is white since its always colorless, carbon is black because of charcoal, sulfur powder is yellow…) his seems counter-intuitive after everything we have just explained.

The inspiration for traditionally coloring oxygen atoms in red is not that clear. It probably has to do with oxygen being required for combustion (and fire is red), or due to the previous fact that we covered: oxygen makes hemoglobin look bright red!

To Sum Up

And that concludes our discussion on this element.

So what is the color of oxygen, you say? Well, the answer is: it depends on its physical and chemical state. It is colorless when in gas form; pale or sky blue when in liquid, and shades of blue, red, and black-metallic when in solid state.

The post What Is the Color of Oxygen: Properties and Exciting Facts appeared first on Chemistry Hall.

We have previously covered in another post how we think AI and machine learning are changing research in chemistry. It is even helping us in the way that we do scientific communication.

But what is digitalization, specifically, and what does it mean for enhancing the way the chemical industry works?

Let’s take a look.

What is Digitalization?

Digitalization is almost synonymous with computerised automation – in fact, “automation” was probably your first thought when you started reading this article. But it’s more than that. Digitalization is also about collecting and processing large amounts of data, and then the outcomes or actions of what that data tells us.

An action can be automated as instructed by specific algorithms and executed by machines, like adjusting pressure or heat, for example. It could also be a strategic policy created by human decision-makers, like a plant manager who decides to request parts for replacement if data shows extreme wear and tear on their equipment.

It’s true that in most cases, digitalization involves data that triggers an automated response. This can be:

• Sensors and devices – the input interface components that measure, scan, or receive information directly from the source. For example, an electronic pressure gauge or a radio frequency identification (RFID) scanner that identifies objects, employee IDs, and equipment
• Edge computing – data processing on the “edge,” which involves speed or safety. The computing happens in the device itself or across various devices. A distributed system controls safety components like a compressor anti-surge loop or a safety integrity loop
• Connectivity – how devices, edge computing, and the Cloud are tied together into a homogenous system despite different specifications and standards. This is about compatibility and communication
• Analytics – the various applications that provide an analytical approach for understanding the results of diagnostics, logistics, inventory, and general trends
• The Cloud – a secure database where data can be stored, accessed, and used by either operators or programs

What Is the Status of Digitalization in the Chemical Industry?

Not all companies have full digitalization infrastructure in place – that’s typically because it’s such a huge investment of time, money, and resources. According to one study, just 4 out of 10 chemical companies expect that their business is more digital than their competitors.

Of all the companies in this survey that are digitalized:

• 40% are using digitalization to become more efficient
• 32% say they are applying digital technology to drive growth
• 11% are using digitalization to meet strategic goals

What Types of Challenges Does the Future Hold?

Despite the drive to modernise, the chemical industry is facing various challenges beyond competition. There are external challenges with complex implications such as those posed by the economy and new regulations.

1. Economic Challenges

There are interwoven and sometimes subtle factors that drive the chemical industry’s position within the economy. Despite recent infusion of capital investment to boost global capacity, the focus is largely on local markets.

Global growth in demand for chemical supplies has decreased, something that is indirectly connected to countries creating self-sufficient energy. Just two examples of this are the fading advantage of the Middle East in terms of oil production and the increasing self-sufficiency of China exerting significant pressure on the chemical industry.

Some level of uncertainty is also faced from end-users. Declining car production, for example, could result in lower demand for specialised automotive chemicals.

2. Regulatory Challenges

Another serious challenge to the chemical industry is to do with regulations. To illustrate this point, let’s think about the many countries that are (rightly) either banning or reducing the use of plastic bags. The process of manufacturing plastics involves chemicals, so this has a knock-on effect on the chemical industry as the overall demand for chemical products such as catalysts or reagents for polymerisation and polycondensation decrease. We’re not saying we should reintroduce plastic bags, by the way! Merely that it will affect the chemical industry.

How Digitalization Will Address these Challenges

Digitalization can help make significant improvements. Aside from raising the standards of competitiveness among chemical companies, digitalization can address the industry’s largest challenges in several ways:

• Cost-cutting – cut operational costs by automating complex manufacturing processes
• Efficiency – machines and workers will become more productive. We’ll save time, effort, energy, and resources
• Quality control – work processes will be more precise and accurate. Errors are minimised or eliminated while high-quality products are produced
• Safety – accidents and injuries can be prevented through continuous monitoring of the various stages of manufacturing. Parameters such as pressure, temperature, and chemical proportions are maintained at safe levels
• Security – monitor the movement of personnel within the facility. Any unauthorised person can easily be detected
• Research and development – data and analytics helps researchers develop new products
• Waste management – toxic materials or hazardous waste can be more easily handled, stored, and disposed of by digitally assessing the ratio of final product to waste
• Customer and end-user analytics – chemical companies will gain new insights to help them better respond to customer demand

Using digital technology to address the various challenges the chemical industry faces is no longer a nice-to-have. Change is inevitable and companies must, quite simply, learn to adapt – and reap the benefits of doing so.

The post What Is The Future Of Digitalization In The Chemical Industry? appeared first on Chemistry Hall.

Especially in the most recent years, many conference lectures by the best research group leaders on chemistry are being recorded and posted publicly online, so everybody can enjoy them and learn about chemistry. All around the globe. Without the need to travel long distances.

Simply thinking about it is amazing! Who could have though that this would be possible >30 years ago. At that time, the possibility of even checking research papers online, did not exist. We did research without the aid of databases on the library.

Now you can access all research that has ever been published online. But not only that, you can also “assist to conferences virtually” from anywhere.

However, not only modern chemistry has been recorded. One of the greatest examples out there of online chemistry talks are the Woodward’s legendary lectures.

Woodward’s Organic Chemistry Lectures

R. B. Woodward won the Nobel prize in chemistry in 1965 for his achievements in the art and science of organic synthesis. In my opinion, he is the greatest organic chemist of all time. He could’ve gotten two more Nobel prizes if he didn’t die so young (1979, at 62), probably due to his contributions to the chemistry of metallocenes and to the Woodward-Hoffmann rules, among many others.

Anyway, he’s been known for giving epic hours-long lectures, explaining the details of his total synthesis. And some of these were filmed at the time! And now, thanks to the internet, are available to watch on YouTube. This is one example:

You can look for a couple more that are around the internet. Even if you are a young chemistry student, if you are interested in organic chemistry, you should take a look. Classical organic reactions that are employed in these >50 years old synthesis are the ones that are usually taught in undergraduate organic chemistry courses.

In any case, watching the master of organic chemistry is an incredible source of inspiration for any aspiring chemist.

The Best Conference Chemistry Lectures Online

As we already mentioned, more and more, we get big conference lectures tape recorded and posted online. These are some of the most enjoyable ones that we have found.

Baran’s Electrifying Chemistry

First off, you can watch and hour-long presentation on synthetic organic electrochemistry by Phil S. Baran, from Scripps Research.

In this lecture, he covers the main reasons behind how using electricity as oxidant/reductant, instead of a chemical reagent is the greenest possible approach for carrying out redox transformations.

New chemical reactivity is being unlocked month after month taking advantage of synthetic electrochemistry. Here, Baran summarizes how he and his research group are pursuing this field of chemistry. He also presents new IKA equipment for carrying out electrochemical transformations in a reproducible manner.

2018 Nobel Prize Frances Arnold

Frances Arnold, from Caltech, won the 2018 Nobel Prize in chemistry for her contributions to the field of directed evolution of enzymes. This lecture is from one year before, in a symposium called “Tailored Biology”.

Her ground-breaking research has to do with modifying enzymes, to make them catalyze chemical transformations that they would not promote naturally, or at least not as selectively.

John Goodenough’s Nobel Prize Press Conference

John Goodenough, a chemistry professor at the University of Texas (Austin), and he is the oldest Nobel laureate of all time!

Prof. Goodenough got his Nobel Prize in chemistry in 2019, as a recognition of his contributions on the development of lithium-ion rechargeable batteries. What’s to say about this discovery? All of us use rechargeable batteries on a daily basis, all the time. We cannot imagine a world without them right now. And one of the main responsible people for these advances is this man. Here’s his Nobel press conference:

The Magic of Chemistry by David Leigh

In 2016, the Nobel prize in chemistry was awarded jointly to Ben Feringa, Fraser Stoddart, and Jean-Pierre Sauvage. They got it for their work on molecular machines, an exploding and revolutionary field within supramolecular chemistry.

Arguably, the fourth key player on this field is David Leigh. He also works on molecular machines. But his lectures are best-known for his personal touch. He is also a professional magician, and brings magic tricks to the chemistry lectures. Apart from presenting some amazing research, the magic makes these lectures some of the best in the world. And you can enjoy and watch one of these online chemistry lectures right now.

The Best Educational Chemistry Lectures

Besides top-tier ground-breaking research conference lectures, you can also enjoy and learn form some more educational resources.

Some More Magical Chemistry

Some of the most both educational and entertaining videos that you can find online on chemistry are the ones by Andrew Szydlo.

He goes though color and phase changes, and he leads students through the world of “playing tricks” with molecules. This might seem like a long video, but I assure you, if you decide to start to watch it, make sure that you don’t have anything to do for the following hour-and-a-half!

Walter Lewin’s Physics Lectures

So we are past chemistry for this video. But I bring it to your attention for two reasons:

• Chemistry and physics are heavily packed together.
• The lectures by MIT professor Walter Lewin are just fantastic, the best educational videos I have ever watched online.

To be fair, when I started studying some physics in college, I didn’t enjoy them that much. That was until I found Lewin’s lectures online. This made love physics almost as much as chemistry.

MIT Lectures from Your Couch

Who said that not anyone in the world can take chemistry lectures from MIT? Now it is completely possible with this and other courses on chemistry offered by this prestigious institution.

Here, this solid state chemistry course is a brilliant example of some of the best online chemistry lectures from a purely educational point of view.

General Chemistry Online Lecture Series (UCI)

This is another example, this time brought to you by the OpenCourseWare of UC Irvine. This is one of the best educational series of lectures on general chemistry that you can watch online.

Periodic Videos!

Finally, we could not end this post with a mention to the Periodic Videos YouTube channel. Here, Sir Martyn Poliakoff and the rest of his team at the University of Nottingham, tackle the most exciting chemistry facts, experiments and questions. Here, every experiment that you alway wanted to perform, but couldn’t, is answered in these videos.

As the title of the site claims, they have covered the entire periodic table, with at least one video on each of the elements. Go on now and check the one for your favorite element!

Closing Up

As you can see, there is plenty of online chemistry lectures that you can explore throughout the internet. These are just some examples, but go ahead and find some more that fit your interests!

Finally, make sure to share your favorite chemistry lectures in the comment sections with us!

The post Watch The Best Online Chemistry Lectures From Your Coach appeared first on Chemistry Hall.

The answer to this question is especially relevant to the younger generations. Will I be able to find a job in 20 years doing exactly what I do now? Am I focusing on a branch of science that will be important in a couple of decades?

For now, it is impossible to predict the future of chemistry. However, it seems very likely that any field of science will evolve significantly with the advances on artificial intelligence.

And this is most likely not avoidable. Computers and robots are here to stay, and they are only getting better. But how much better can they become in our lifespan?

Artificial Intelligence and Machine Learning

Probably one of the biggest revolutions in science is the appearance of computers. Something that today we take for granted, has pushed the speed of scientific discovery for the past decades.

Today we almost cannot conceive synthetic chemistry without tools such as SciFinder or Reaxys. But how long until you can input a molecule that has never been made before in a search box, and you get exactly the steps you need to take to make it in a lab? Artificial intelligence (AI) and machine learning might be behind this through the future of chemistry.

If you are not familiar with those terms take two minutes to watch the video below:

You can teach a computer how to differentiate a cat from a dog.

Using AI to solve this problem is not very useful, since humans are already pretty good at it. However, when it comes to analyzing hundreds or thousands of data points at the same time, human beings are drastically outperformed by computers.

And, in a way, chemistry is a lot about this.

How Can the Future of Chemistry Be Defined by AI?

When you want to optimize a new synthetic step, or the properties of a new material, what do you usually do?

Dive into SciFinder, download a couple of reviews and 10 research papers, skim over the schemes, and from that, extrapolate the conditions you want to test in the lab.

Seeing it from an AI perspective, this procedure is extremely rudimentary, to say the least. And yet it’s what >90% of experimental chemists (as myself) do on a daily basis. And computers will eventually be better at it, no doubt about that.

Obviously there is a significant creativity component of a research jobs. And identifying or dealing with unknown results. At the early stage of AI and machine learning in which we are at, humans still outperform machines. It is difficult to know how long it will stay this way. Honestly, I’d be surprised if it took more than 10–15 years.

The Future of Chemistry Now

AI has been around for several decades. Getting better and better every day.

Computer-assisted chemical synthesis was pioneered by E. J. Corey as back as 1985, when he reported in Science a very basic system for synthetic analysis in organic chemistry. This was 5 years before being awarded his Nobel prize, in 1990, but there was not a big follow up on this kind of chemistry until more recently.

However, in the past couple of years, an explosion in computer-assisted chemistry is only getting started. This has been commented by F. Peiretti and J. M. Brunel in 2018, but even since that day, many more recent works have seen the light of day. This might indeed define the future of chemistry.

Some of the key players on this approaches are Abigail Doyle, Matt Sigman, Lee Cronin, or the MIT team led by Timothy Jamison and Klavs Jensen. We will try to briefly review some of the very last years.

We apologize in advance in case we missed some important work. This is not intended to be a comprehensive review, but rather just a collection of some examples to illustrate the idea.

Parameterization and Prediction

The research group led by Matthew Sigman at the University of Utah has plenty of collaborative projects based upon parameterization and prediction.

This method is based on applying predictive statistical analysis to chemical reactions. They part from MM and DFT calculations to abstract properties or parameters of ligands or catalysis. Then they run statistics comparing these parameters to the experimental results obtained with each ligand or catalyst. They come up with models that allow predicting how other ligands, catalysts or substrates would behave.

It apparently it works!

A recent example is a collaboration with Mark Biscoe, in which they show how ligand parameterization allows finding the best ligands to perform a enantiodivergent (you can choose the enantiomer you want as product just by tuning the ligand) Pd-catalyzed C–C cross coupling reaction.

Holistic Predictions of Enantioselectivity

In 2019, Reid and Sigman reported a ground-breaking report on a model for holistic predictions of enantioselectivity in asymmetric catalysis.

As we stated in the introduction, a big part of a synthetic chemist job is to scan the literature to select some reaction conditions to test on a new substrate. This is clearly a job that a well-programmed computer should do better than a human being, especially when there are hundreds or thousands of possible conditions available.

This is a field that Sigman is pioneering, and awesome trends which allow for very significant predictions have already resulted from their efforts.

Many say that statistics, AI and machine learning could be the future of chemistry.

Machine Learning for Predicting Chemical Reactions

As Doyle group explains on their website, machine learning (which is basically statistics and computer science) can be the tool that will solve the problems of multidimensionality (which makes complex problems impossible for humans to analyze) inherent to chemical reactivity and structure.

In early 2018, Doyle reported in Science a collaborative work with Merck in which they developed a chemical model based on machine learning. They used a random forest model to predict the outcome of C–N cross coupling reactions.

Studying the Influence of Additive by Machine Learning

They mainly studied the influence of an additive (a family of isoxazoles) in one of the most useful reactions out there, the Buchwald-Hartwig amination.

A set of 15 different isoxazoles were used as “training set” (to obtain the linear regressions), and then another 8 of them were used as “test set”. Some examples are shown below, together with the corresponding regressions. As you can see, the data obtained with the test set correlates well with the “training regression”. Meaning that a good level of prediction is achieved.

Teaching Computers How to Do Fluorination

A similar concept was reported later that year by the same group, in which an awesome combination of HTS (high throughput screening) experiments and machine learning allowed developing a predictive model for the fluorination of alcohols with PyFluor. This resulted in a great expansion of the scope previously reported by Doyle and co-workers.

In the left, a schematic example of the type of HTS experiments run is displayed, showing how changes on the fluoride source and the base drastically affect the reaction yields.

The right graph shows all the results of observed yield vs. predicted yields. Very good correlations are obtained.

Are Robots Going to Take Our Jobs?

If by “our jobs” you mean by exclusively technical lab work as a chemist, the answer most likely.

But don’t get me wrong, I am nothing but optimistic about the future of chemistry. We need to embrace tools such as AI or robotics. They are here to free us from the most boring routine part of research, so we can focus in creativity to solve important problems.

On this particular matter, several research groups have been working on designing and constructing a chemical robot.

The Chemistry of the Future: Merging AI Planning with Robotic Synthesis

Timothy F. Jamison and Klavs F. Jensen from the Department of Chemistry of the Massachusetts Institute of Technology (MIT).

In 2018, they presented in Science their first version of a chemical synthesis robot. The basic idea of this machine is a complex flow chemistry system controlled by a software that allows optimizing multiple variables. So you can literally input the parameters that you want to optimize, feed the reagents, and wait until your optimization is complete. Then in a matter of days the scope of your transformation is also done.

This is how this synthesis robot looks like:

Fast-forward only one year, and this beast is where they are at:

The same MIT team published a couple of days ago a completely next-generation version of this chemical robot.

Now it is not just about chemical optimization. The synthetic system is fully integrated with an AI planning software.

This AI software is based in what we discussing over the entire article: taking data points out of thousands of published reactions, feeding them to complex algorithms, and getting optimal synthetic routes for a new or relevant target compound.

One can imagine that the third-generation of this system might even come up with its own ideas of what to synthesize. Who knows how far away we are from that…

The Future of Chemistry: Discovery Supported by Chemical Robots

The last example is mainly based upon flow chemistry systems. But some reactions are not suitable for flow. Traditional lab-scale organic synthesis is something that the Cronin group wanted to “digitalize”.

Leroy Cronin and co-workers have published in 2018 their views on howcan we use algorithms to aid discovery by using chemical robots. Not long after, in early 2019, this group working at The University of Glasgow reported some of their efforts on making such robot.

Cronin’s “Chemputer” is a modular robotic platform that allows carrying out the four basic steps of organic chemistry: reaction, work-up, isolation and purification.

For this purpose, it is equipped with pumps, reactors, filtering systems, automated separatory funnels, a rotavap, and of course, software to control all the process.

The following video allows getting an idea on how this system works:

This new system based on a “chemical programming language” allowed the synthesis of several medically relevant molecules, such as sildenafil or rufinamide.

Computer-assisted Total Synthesis of Complex Natural Products

You can argue that the targets selected to test the synthetic systems described above are not of very high complexity. Typical natural product synthetic problems tackled by the big groups are much more challenging.

But computers can also assist us with those! It is just a matter of how well can we integrate DFT-based high level computations with the methods described above. This kind of integration will be relevant in the future of chemistry.

An example of such prediction is the recent synthesis of Paspaline A and Emindole PB by Timothy Newhouse and co-workers.

In this work, the authors envisioned a biosynthetic approach to those natural structures, and though of 3 possible potential intermediates. All these 3 intermediates could in principle lead to the desired natural products.

But the chosen intermediate would have to cyclize with the appropriate selectivity. In case it didn’t, the synthesis of the corresponding intermediate would have been in vain (a problem that every chemist working on natural products synthesis has encountered).

As you can see below, the proposed structures are fairly similar, it would be almost gambling for a human being to predict the outcome of each cyclization. But the structural differences make them difficult to synthesize from a common intermediate.

First Steps on the Natural Products Chemistry of the Future

To tackle this problem, Newhouse’s group predicted via DFT calculation which of the three would cyclize the way they wanted. Once they had their theoretical answer, they prepared only that intermediate precursor (saving 2/3 of the synthetic efforts required). It ended up behaving as predicted, and they completed the total synthesis.

Before Newhouse, the group of Richmond Sarpong and co-workers had already applied a similar concept. They reported in 2015 the use of network-analysis to guide the retrosynthesis of very complex natural products.

Sarpong’s group applied network-analysis iteratively at the early stages of the synthetic planning of weisaconitine D and liljestrandinine, published in Nature. This allowed to come up with efficient disconnection

Even more recently, the same group of researchers published in J. Am. Chem. Soc. the total synthesis of the diterpenoid alkaloid arcutinidine.

This synthesis was also aided by this network-analysis, which is inspired by the initial work already performed by E. J. Corey back in the 80s.

I wanted to close with this last set of examples, because they are a great demonstration of what, in my opinion, would be the ideal future of AI and computing in organic chemistry.

“As scientists, AI should not replace us, but rather free us from routine and boring tasks, letting us focus on what is important: solving more complex and more important problems.” Click to Tweet This

I would love to hear from your opinion on AI and computers, and how they are going to affect how we see and approach chemistry (and science in general). After all, the future of chemistry is in our hands.

Feel free to post in the comment sections below!

The post What Is the Future of Chemistry? [Artificial Intelligence in Science] appeared first on Chemistry Hall.

Some of the most well-known forms of carbon are diamond (a) or graphite (b). Other allotropes are fullerenes (d, e, f), amorphous carbon (g) or carbon nanotubes (h).

But until today, it was not possible to characterize a cyclic molecular all-carbon ring. Researchers at University of Oxford teamed up with scientists at IBM, and resurrected this long-forgotten challenge.

The result is spectacular: a circle of 18 sp-hybridized carbon atoms, held together by alternating single and triple bonds.

The challenge of building such molecule is actually not new. In fact, the basis for this recent work were already established in 1990.

Initial Work Towards Cyclocarbon

At that time, while pursuing the synthesis of the same kind of cyclic carbon allotrope, cyclo[18]carbon, the group of François Diederich reported in the Journal of the American Chemical Society the synthesis of and characterization of a stable hexacobalt complex of this cyclic material.

This structurally peculiar coordination complex may seem to be really close to the desired all-carbon cyclic molecule, but this couldn’t be further from the truth.

In fact, almost 30 years passed since Diederich and his team made the initial steps towards this target, until today.

Synthesis and Characterization of the First Cyclic Carbon Allotrope

Fast-forward to 2019, P. Gawel, H. L. Anderson (Oxford University), L. Gross (IBM) and co-workers finally completed this challenge.

How did they do it? Basically they made a great use of Scanning Tunneling Microscopy (STM).

STM is a technique based in quantum tunneling. In STM, you usually deposit the molecule you want to study in a metal surface. Then a voltage is applied through a very small conducting tip, which allows electrons to “tunnel”, generating a current. Analyzing changes in the system, you can extract information and display it as images.

Thanks to the most recent advances in STM and atomic force microscopy (ATM), it is possible to obtain and see images of molecules with great resoluion.

Diederich group had developed the synthesis of several cyclocarbon oxides (shown as precursors in the pictures below).

Cyclocarbon oxide (C24O6), a triangular oxygenated molecule, was deposited on a bilayer of NaCl on a Cu(111) surface. Then it was submitted to low-temperature STM-AFM.

Under these conditions, the starting molecule loses CO as carbon monoxide. This process can occur multiple times, until the all-carbon 18-membered ring, cyclocarbon, is obtained. The molecule can be imaged in-situ (and therefore, characterized) at the same time. In this manner, the first cyclic allotrope of carbon was finally prepared.

The decarbonylation process takes place step by step (one molecule of CO at a time). This allows not only to see images of the final cyclocarbon, but also of several decarbonylated intermediates.

It is hard to tell if the resulting structure is “aromatic”, since classical Hückel rules cannot be applied to such complex systems. In fact, one could argue that this product is borderline between inorganic and organic chemistry.

Many scientist had tried before to make and observe this elusive structure. But why?

The Significance of the First Cyclic Carbon Allotrope

Well, for starters, initial studies on cyclo[18]carbon suggest that this new material can act as a semiconductor, which is the main appeal for the synthesis of new carbon allotropes, or other compounds such as polyaromatic hydrocarbons.

From a purely academic point of view, this specific structure is significantly less stable than any other of the well-known carbon allotropes. Therefore, it was a significant scientific challenge to overcome. It took 30 years and mastering modern techniques such as STM-AFM to actually see a molecule that many didn’t think we would see any time soon.

This discovery also allowed scientist to solve an old mistery. Are cyclic all-carbon molecules polyynic (alternating double and triple bonds) or cummulenic (consecutive double bonds)?

As you can see in the image below, the experimental image of the cyclic allotrope of carbon, perfectly matches with a predicted polyyne, made of alternating triple and single bonds.

So far this is very fundamental research, since these techniques only allow making “one molecule at a time”, and at under very specific conditions. This doesn’t allow actually preparing enough amount of material to test potential applications. However, this is a big leap forward in nanomaterials chemistry, and for sure this discovery will lead the scientific community to many relevant findings.

All credit to:

An sp-hybridized molecular carbon allotrope, cyclo[18]carbon. K. Kaiser, L. M. Scriven, F. Schulz, P. Gawel, L. Gross, H. L. Anderson Science 2019, doi: 10.1126/science.aay1914

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Confirming the actual structure of a molecule, is still a big challenge now-a-days. The advances in techniques such as NMR (Nuclear Magnetic Resonance) spectroscopy, or single-crystal X-ray diffraction have significantly helped speeding up this problem.

Molecular structure determination

Every month we get reports of chemical structures whose structures have to be reassigned or revised after some study (either synthetic or just based on characterization techniques) is carried out. On this regard, it is worth remarking the difference between scientific models and reality.

Truth is, even today, the methods for the characterization of molecules available to use routinely (which are explained in the most basic chemical bibliography), can be consider rather rudimentary, and of difficult interpretation for non-experts. Let me be honest, I am a trained PhD organic chemist and if I had to take a look at the NMR spectra of a complex natural product such as maitotoxin, I would probably have no clue what I am looking at.

Single crystal X-ray diffraction is probably the closest method to easily visualize the structure of a molecule in 3D. However, this is not a bulletproof method. The sample preparation (growing single crystals) required for this indirect technique, renders it useless for a wide variety of chemical compounds.

Can we actually see real molecules or atoms?

Accordingly, I would say that by today, there should already be a method that allows taking a direct microscopic “picture” of any compound you like, and immediately visualizing its structure in a screen. Apparently we are not quite there yet (in regards to “any compound”, keep reading). However, the answer may come under the name of atomic microscopy, and all of its variations.

Atomic force microscopy (AFM) or scanning force microscopy (SFM) is a very high resolution probe-microscopy technique. It allows us to actually “see” or “take real pictures” at the nanometer-scale, in which the molecular realm lies. A picture is worth 1000 words. In the example below, scientists make use of this technique to get pictures of a compound called naphthalenetetracarboxylic diimide. We can actually see a real molecule.

Much more recently, researchers at Oxford and IBM used STM-AFM to generate and visualize in situ the first cyclic allotrope of carbon, cyclo[18]carbon.

Seeing atoms in motion

The world of visualizing at the atomic level took a leap more than ten years ago. In 2008, a research group reported the imaging for the first time of light atoms and molecules on graphene. Subsequently, the same team managed to observe for the first time the actual movement of insolated graphene atoms in real time. The following movie from the Berkeley team shows the growth of a hole in a graphene sheet. For this experiment, a beam of electrons is focused to a specific spot on the graphene sheet, blowing out the focused carbon atoms making a hole. Besides, it can also be observed how the carbon atoms rearrange themselves (edge reconstruction) to adapt a more stable configuration.

The Boy And His Atom: The World’s Smallest Movie

The Guinness World Record for the “Smallest Stop-Motion Film” is held by a movie recorded by IBM scientists. Sometimes, nanophysicists also need to have a bit of fun, and what they decided is to “film” a movie by using scanning tunneling microscopy, a the result is in the following video:

By the use of this technique, the scientists managed to move a lot of molecules of carbon dioxide following their will. The result is a movie you can only see using a microscope that magnifies one hundred million times.

Direct observation of chemical reactions

Obviously, taking real pictures of molecules and atoms was just not enough for the scientific community. If we fast-forward to year 2013, atomic microscopy, more specifically, non-contact atomic force microscopy, allowed the direct imaging of molecular structures during a chemical reaction. Some results of these experiments published in the journal Science are displayed below. We cannot only see actual atoms molecules, we can observe directly chemical reactions!

AFM in structural determination

This field started as a cluster of isolated cases, but as the years went by, more and more examples of the application of this set of physical techniques are being constantly reported. The level at which the studied molecules can be observed is rather impressive. A recent example is the actual structural determination of a natural compound, breitfussin A. Several functional groups of the molecule were derived from classical spectroscopic data (a). Then, an AFM image (c) allowed observing the real structure of the molecule, placing each piece of the puzzle (a) in the correct spot. This established the previously unknown structure of the molecule (b).

Taking real pictures of complex chemical reactions

On the reactivity side of things, much more recently, it was possible to directly image the course of a reaction called the Bergman cyclization. This is one of the most fascinating rearrangements in chemistry. The chemical transformation is directly induced in the metal surface in which the atomic microscopy procedure is carried out.

However, as stated at the end of the introduction, not every molecule or reaction can be a candidate for a STM study as these. Several conditions need to be met. One of them (which might have already called your attention) is that the analyzed compounds need to be near-planar. These techniques rely on depositing the molecules of the compound in a planar metal surface, so planar molecules are the ones that give more interpretable data.

The search for the “Holy Grail” of structural determination

To finish this short essay that does not make justice to the whole field of molecular imaging, a recent application of what is called micro-electron diffraction (MicroED) will be discussed. This brilliant application of electron diffraction, allows overcoming probably the biggest problem on classical X-ray diffraction methods: the requirement of crystalline material of the molecule which structure wants to be elucidated.

This technique allows taking simple powder of any non-crystalline solid, without almost any sample preparation, and getting 3D structures of the powder nano-crystals in a matter of minutes, with extremely high resolutions. The structure of molecules with very high complexity, as thiostrepton, could be obtained unequivocally.

Is this the future of chemistry?

Can we see real atoms and molecules at this point? I would say that we definitely can. All the results that have been described in this article were published only over the last decade. Atomic microscopy seems to be here to stay, and it might be one of the tools that finally allows chemists to stop relying in rudimentary techniques for the determination of molecular structures. Only time will tell.

Stay tuned for more posts about the future of chemistry, share, and post your thoughts in the comment section!

The post Can We See Real Atoms and Molecules? Electron Microscopy at a Glance appeared first on Chemistry Hall.

Lysergic acid diethylamide, commonly known as LSD, and colloquially called acid is a psychedelic drug which was first synthesized on November 16^th, 1938 by a chemist called Albert Hofmann.

Do you want to known everything about the discovery and total synthesis of LSD? Keep reading!

LSD was discovered in Switzerland, but it was not until 1943 that the special properties of the compound were found. Today we do not focus on chemistry concepts but rather on a historical landmark. You might know a bit about LSD, but you also probably don’t know much more about its discovery and synthesis. That’s what we are going to fix in this article, it is a very interesting story and of course we will be covering a remarkable total synthesis!

When it was discovered by Sandoz Laboratories, the purpose was using LSD as a respiratory and circulatory stimulant. It was found while analyzing organic compounds obtained from the ergot fungus and the medicinal plant squill.

LSD is well known for its psychological effects, which can give rise to closed- and open-eye visual hallucinations, alter the thinking process and the sense of time or, to sum up, induce abnormal psychic states. But as we have already seen, all of these properties were found no less than five years after its discovery, by the same guy who first synthetized it, Albert Hofmann. He was the first person to ingest and experiment the effects of the drug. The Telegraph newspaper placed him on the first position in a list of the 100 greatest living geniuses. The discovery of the psychoactive properties of LSD was a bit of a coincidence, since the Swiss chemistry accidentally absorbed a very small amount of the compound (the threshold dose is only about 20 micrograms) through his fingertips, finding these effects by himself. He also described how he was felling:

“…affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After about two hours this condition faded away”

The synthetic route that Hofmann used to prepare LSD is rather simple; the structure of the drug was very similar to the compounds extracted from the ergot fungus. He used ergotamine as starting material, so most of the structural work was already done by nature. We will focus in this article on the total synthesis of the drug, which means, a synthetic route that can be performed starting off from simple chemicals and reagents that are commercially available.

The newly-discovered physiological properties of ergot fungus also took Arthur Stoll attention, who also played a really important role on the early study of this family of compounds. He isolated and studied products such as ergotamine, ergonovine (the simplest one) and so on.

Growing Interest on the Synthesis of Lysergic Acid

The interest on the synthesis of lysergic acid rose from the discovery of all these compounds which had that part of the structure in common. The whole structure was not resolved and confirmed until 1949. However, it drew the attention of many organic and medical chemists anyway. Once the properties of LSD were found, this interest increased even more.

The first LSD synthesis was published on 1956, by one of the greatest (if not the most) organic chemists of all times, Robert Burns Woodward, born in Boston, Massachusetts. He is considered to be the best organic chemist of the 20^th century, in terms of experimental and theoretical studies of chemical organic reactions. He also received the Nobel Prize in chemistry in 1965 for his synthesis of complex organic molecules. One of these molecules was lysergic acid. We will review his synthetic route as it deserves to be done. Also, we will cover the mechanism for each of the steps of this LSD synthetic route, in order to make it as instructive as possible for organic chemistry students. The original publication by Woodward can be found here.

The synthesis of lysergic acid presented an important problem: the high reactivity of its indole group. This heterocycle was considered so far incompatible with any long synthetic procedure. So, to avoid this problem, Woodward’s group decided to base most of the route on dihydroindole compounds (just like indole, but with 2 more hydrogens, and one double bond less), and transform it into the indole of LSD later one.The starting material of the whole route was β-carboxyethyldihydroindole, protected with a benzoyl group at the nitrogen.

The First Step: Ring C Formation

The initial compound was treated with thionyl chloride, converting it to the corresponding acid chloride. This makes the carbonyl group highly electrophilic. Then, the molecule undergoes an intramolecular Friedel-Crafts acylation reaction after the addition of aluminum chloride, assembling the ketone shown in the picture above.

Elaboration of the New Ring

The most problematic part of the synthetic route was the formation of ring D of the compound. Since they needed to add a substituent to the α-carbon to ketone carbonyl, a bromination was performed with some nasty molecular bromine in acidic media.

The desired brominated compound was obtained in a very good yield, but the first attempts to continue the synthesis from here failed. Many substitution reactions at the alkyl bromide failed.

However, after many unsuccessful attempts (and some successful but in rather poor yields), it was found that treating the brominated intermediate with methylaminoacetate ethylene ketal in a non-polar solvent, gave the desired alkylated intermediate in an excellent yield, which could be hydrolyzed using HCl to deprotect the acetal (releasing the ketone). At the very same time, the benzoyl group that protects the dihydroindole is also removed.

Finishing The Tetracyclic Core for the LSD Synthesis

The next step is the formation of the heterocyclic ring D, which was achieved effectively treating the last ketone intermediate with sodium methoxide in methanol.

The mechanism of this step is basically the formation of the kinetic enolate of the most accessible methyl ketone and then, nucleophilic addition of this enolate to the other ketone, closing the third and last ring of the molecule. This is immediately followed by an elimination reaction, giving rise to the corresponding α-β-unsaturated ketone.

The treatment of this compound with sodium borohydride and sodium anhydride subsequentely reduces the ketone group to the alcohol, and protects the nitrogen of the dihydroindole. Next, they substituted the freshly introduced alcohol by a chloride. It was found that treating the alcohol with thionyl chloride in sulfur dioxide (liquid) gave the desired intermediate in good yield.

The obtained chlorinated intermediate was found to be very susceptible to hydrolysis to yield once again the alcohol, so the next reaction had to be performed fast and in special conditions: treating the compound with an excess sodium cyanide in anhydrous liquid hydrogen cyanide (pretty scary thing!). Anyway, Woodward’s group managed to make the reaction work and the resulting intermediate was treated with acidic methanol, to give the corresponding methyl ester. Also, the acetyl protecting group on the nitrogen was removed under the acidic conditions.

After this the product was hydrolized to give the corresponding carboxylic acid.

Now the work was almost done! The only remaining task to obtain lysergic acid was the formation of the oxidation of the dihydroindole to indole selectively. Some considerably obscure reaction conditions were employed, based on the use of Ni Raney and sodium arseante. This led to the desired indole (which is already lysergic acid), leaving untouched the rest of molecular functionalities.

Lysergic acid was obtained as a racemic mixture which could be separated by chiral resolution.

Final Amidation of Lysergic Acid to Give LSD

However, this does not complete the synthesis of LSD. The last step is the formation of an amide bwith diethylamine.

The following are the reaction conditions used by Shulgin to obtain LSD from lysergic acid:

Alexander “Sasha” Shulgin was an American chemist author of the famous book PiHKAL: A Chemical Love Story (Phenylethylamines I Have Known And Loved), and its continuation, TiHKAL (Tryptamines I Have Known And Loved), where he makes a detailed explanation and analysis of how he discovered, synthesized and personally bioassayed a huge variety of drugs, all by himself (with the assistance of his wife, Aten Shulgin). He died less than a year ago, June 2, 2014 (aged 88), and with this last reaction I intended to make a small tribute to this great medicinal chemist, biochemist and psychopharmacologist.

You can PiHKAL books through Amazon, I promise they are worth a read!

“LSD,” -writes the chemist Alexander Shulgin– “is an unusually fragile molecule… As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely.”

But of course, this is not the end of the story… Organic chemistry and synthetic techniques have advanced A LOT from those years to present, and way better methods have been published to prepare lysergic acid diethylamide from scratch in a more efficient and easier way.

Modern LSD Synthesis Routes

A very recent route for the total synthesis of LSD is that published by Tohru Fukuyama et al. from the Graduate School of Pharmaceutical Sciences, University of Tokyo, in 2013.

This LSD synthesis is based on the Evans aldol reaction, which allows a stereoselective construction of the needed chiral center followed by a sequential process, which includes a metathesis reaction that produces the ring-closure and finally a Heck reaction which finishes the construction of the two rings.

To finish this article, I would like to say that this is just an example of the discovery, isolation, preparation and development of a new kind of drug, and many others have been discovered over the years, which have saved and improved (and of course, still do) the life of humanity. The fact that LSD can be used as a recreational drug is not the topic of this review.

I enjoy organic and medicinal chemistry a lot (it is actually a part of my life, what I studied and what I work on every day), and I love writing this kind of articles. Please, do share your thoughts, criticism, or suggestions in the comments, it will be really appreciated. Feedback encourages us to keep working on Chemistry Hall!

Organic chemistry can explain a great deal of things. If you want to take a look at another real-world chemistry story, I’d recommend you to dive into why urine smells bad after eating asparagus, as we covered in another post.

Also, if you have any suggestion or idea for future posts, it will be strongly valued too!

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