The ineluctable requirement for the trans-iron elements molybdenum and/or tungsten in the origin of life #chempaperaday 271

An evolutionary tree of key enzymes from the Complex-Iron-Sulfur-Molybdoenzyme (CISM) superfamily distinguishes “ancient” members, i.e. enzymes present already in the last universal common ancestor (LUCA) of prokaryotes, from more recently evolved subfamilies. The majority of the presented subfamilies and, as a consequence, the Molybdo-enzyme superfamily as a whole, appear to have existed in LUCA.

I believe many people know that some enzymes have molybdenum cofactors. But, I highly doubt that many are aware of the fact that tungsten can also be found in some enzymes. Which one came first though? What are the differences between them in terms of solubility for example? The real interesting part is that both molybdenum and tungsten are produced in supernova explosions. So when did they come? How did they come here? how did they affect the life on earth? Well not all the answers are known yet, but here is a nice paper on molybdenum and tungsten enzymes.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278043/

Elements and Evolution #chempaperaday 270

Changes in elemental abundances in Earth's oceans on geological time scales are intimately linked to evolutionary processes.

 The concentrations of metal ions in the oceans (and in the earth's crust)  have changed dramatically since the beginning. It is clear that they assisted the life on earth. All these are also tied to atmospheric conditions such as the concentration of certain gases and the temperature. 

If you are into evolution and the elements' effects on it, this is a good start.

http://science.sciencemag.org/content/322/5907/1481

Redox bifurcations: Mechanisms and importance to life now, and at its origin #chempaperaday 269

Some of the biological reactions don't really make sense in terms of redox chemistry. Most of the time, these reactions occur because they are catalyzed by enzymes or coupled to other mechanism. Here is an interesting Commentary about these processes and how they approach the the topic. Worth reading.

http://onlinelibrary.wiley.com/doi/10.1002/bies.201100134/abstract

Metallocenter Biosynthesis & Assembly #chempaperaday 268

It's generally accepted that about 30% of proteins are metalloproteins, and metal ions in these proteins have several different roles. I will not go into that. For a long time, I have been really interested in one thing in particular: how do these metal ions find their ways to these proteins? Cells have several different metal ions, what really brings a particular metal ion to a particular metalloprotein? Metal ions at different oxidation states have different radii, but some of these are very similar to each other. How come one is swapped by another? What regulates all these? In fact, I should call myself lucky because I asked some of these questions to Harry B. Gray in person. But, reading the literature and really learning is such a different thing.

Well all the questions above and many more can be answered by this amazing book chapter. It's a perfect introductory text for people interested in metals in biology. Here is the abstract :

Cells synthesize biological metallocenters by use of several recurring themes, often with multiple themes combined into a single pathway. In the simplest situation, binding of a metal ion to a biological ligand occurs by reversible thermodynamic control; however, the prevalence of metallocenters deeply buried within macromolecules, the exceedingly low concentrations of free metal ions within cells, and the sophisticated structures of many metal-containing active sites and cofactors provide evidence that alternative and more complex approaches must also exist. In some cases, metal binding is accompanied by posttranslational modification of the target protein, either before or after the metal binds. Many metallocenters contain additional components that are added along with the metal ion. In other cases, metallochaperones are used to deliver the metal of interest to an apoprotein. Another alternative is to incorporate the metal into a protein subunit that subsequently swaps for an apoprotein subunit in the native protein. In addition, electron-transfer reactions may be coupled with metal assembly. Other proteins require a preassembled metal-containing cofactor rather than just the free metal ions. The cofactor may bind reversibly or be delivered by a chaperone, and scaffolding proteins may be used to provide a framework for construction of such a cofactor. Covalent attachment of the cofactor occurs in some cases. Finally, molecular chaperones that directly or indirectly alter the conformation of the target apoprotein may be utilized. In many cases, the function of the molecular chaperone is coupled to nucleotide triphosphate hydrolysis. Examples are provided for each of these metallocenter biosynthetic mechanisms.

http://onlinelibrary.wiley.com/doi/10.1002/9781119951438.eibc0257.pub2/abstract

What is wrong with this periodic table?

Here is an interesting periodic table from the journal Cell. The title is definitely interesting and I really want to read the article. But, I can't help but staring at this periodic table.

First of all, the d-block has 11 groups instead of 10. A whole group (either 17 or 18, you pick one) is missing. Finally, the f-block has 15 groups. I am not sure but it looks like there are 118 elements in total which is fine. But, you don't see a periodic table like this often. I am wondering if any of the authors or an editor ever noticed anything wrong with this. I am also wondering where they got this periodic table from.

I think it's open access, so go ahead and look at it.

http://www.cell.com/cell-reports/pdf/S2211-1247%2816%2930297-2.pdf 

 

Genetic Optimization of Metalloenzymes: Enhancing Enzymes for Non-Natural Reactions #chempaperaday 267

Bioinorganic catalys is not that new but "artificial metalloenzymes" as it is called is a relatively new research area. But, I think it is one of the most amazing ones. Just think about it, you genetically modify an enzyme to do something else or to do something extra! How cool is that? For beginners, it is a nice review and starting point to dive into that world. Many examples of these enzymes and how single modifications can show dramatic effect on reactivity or selectivity.

It's open access!

http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201508816/abstract

The 4s and 3d subshells: Which one fills first in progressing through the periodic table and which one fills first in any particular atom? #chempaperaday 266

Electron configuration of transition metals sometimes get complicated due to some "irregularities". If you have NEVER noticed this, look them up in an inorganic textbook. This paper doesn't really give you anything new if you already know the underlying reason for those configurations. However, the authors did a computational experiment to show us which orbitals are more stable upon adding an electron. So, that's useful in terms of teaching.

The summary is that  "there is no scientific reason to write the electron configuration of transition elements as [Ar] 4s 3d and the correct form is [Ar] 3d 4s."

http://link.springer.com/article/10.1007/s10698-016-9249-0

Reproducibility in density functional theory calculations of solids #chempaperaday 265

People probably won't like what I will say, but why is this a Science paper? For your information, I respect the work here in this paper. I just don't understand what makes it a Science worthy paper. I am someone who uses DFT all the time to the complexes I synthesize. They have hundreds of atoms, and at least two metal atoms (usually in unusual geometries and oxidation states). When one method or basis set doesn't work, you try another one; and it goes on... Anyway, maybe I am just too stupid to understand the science behind this paper.

http://science.sciencemag.org/content/351/6280/aad3000

A brief history of cancer: Age-old milestones underlying our current knowledge database #chempaperaday 264

Cancer is not a new disease. It's been around since life on earth started. I found this Minireview very useful, and it can definitely be used as a source by following the works cited. The authors compiled several early examples of cancer, and they provided us some writings from ancient philosopher/doctors about the disease. The really frustrating part is that for some types of cancer we are not in a much different situation than that of those ancient doctors. 

In the end of the article, there is also a nice timeline of cancer with "milestones".

http://onlinelibrary.wiley.com/doi/10.1002/ijc.29134/full

How much chemistry (history) does C&EN know?

Yesterday I saw a link to a chemistry history quiz by C&EN magazine and I decided to take it. The second question asks the first "human made" element and the answer according to C&EN is plutonium which is WRONG.

 the screenshot from the related quiz question and answer

 

Assuming that they really are asking the first synthetic element, I guess every chemist (apparently except the one prepared the quiz) can tell you that technetium is the first synthetic element, hence the name. I am not sure if C&EN is bothered to learn the truth, but there you go people. 

I am not sure if I am missing something, but it's hard to believe that they got this fact wrong. Please correct me if I am wrong.

Charles Darwin - not a genius?

A few weeks ago, we had to evacuate the department for some reason. As I was hanging around some old Science magazines, I found the Jan. 9, 2009 issue. It appears that it's a special issue dedicated to Charles Darwin and his famous book. I read several articles in this issue and I'm glad we evacuated the department.

Recently, I saw this ridiculous article "Charles Darwin was no 'heroic genius', say scientists". Thanks to modern day "science journalists", it was hard to find the original research article. Anyway, I was able to find the paper with some digging. I am not planning to read the paper since I have better and more useful things to do. Assuming that they do claim that Charles Darwin was not a genius and he was just someone who followed up a popular idea of his time, I am flat out going to say that I disagree. This brings us to the Science magazine I mentioned above. Please take a few minutes and read why he was special. Thanks to Peter J. Bowler there is an article in this issue with the title "Darwin's Originality". You'll find the answers you need there. I hope Dr. Michael Muthukrishna (the lead author of the claim above) who is I guess a psychologist will find some time to read this article and hopefully change his mind. Here is what he said to Telegraph :

"We can see this process at work when two people have the same apparently innovative idea at the same time – such as Charles Darwin and Alfred Wallace with the theory of natural selection."

Rather than being heroic geniuses, Darwin and Wallace were in the same ‘cultural milieu’, both reading the same books and both travelling to biologically diverse island environments.”  

Looks like it's that simple for Dr.Muthukrishna. Ridiculous.

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty-Chemicals Manufacturing #chempaperaday 263

This is a minireview where the authors focused on the implementation of metathesis catalysts "in specialty-chemicals and pharmaceutical manufacturing". I think it is a very useful review. In particular, I like the details like the effect of impurity (and what they are). These impurities are not only coming from the previous steps or starting materials but they are also some of the undesired side-products of metathesis. Early metals such as Mo and W tend to cleave and make new bonds. So, as you can imagine there is a lot more going on these reactions. 

There is also nice table where you can see a long list of ring closing metathesis (RCM) catalysts and their industrial application. Finally, there are several examples of RCM, the challenges and some nice discussion about their activity and selectivity. 

http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201506846/abstract

Bidentate Ligands on Osmium(VI) Nitrido Complexes Control Intracellular Targeting and Cell Death Pathways #chempaperaday 262

Among the group 8 anticancer complexes, you see mostly ruthenium-based ones. But, this doesn't mean that ruthenium is unique or osmium doesn't work. In a series of posts, I'll focus on osmium complexes that show anticancer activities. Here is the first one. 

In this article, there are a series of osmium(VI) complexes and two of them show two different mechanism of action. And as the authors say one of them is "the first osmium compound to induce ER stress in cancer cells."

 http://pubs.acs.org/doi/abs/10.1021/ja4075375

Social media and science

I rarely write anything on "controversial" topics. A few days ago, I saw this interview was mentioned here and there. I usually don't read young scientists' interviews since I don't think I can learn much from them. How much experience they have anyway? Let's see what people especially didn't like about this interview:

- Do you think there is an increased need for scientists to market themselves and their science as a brand? 

I think the idea that scientists need to operate more like a business is becoming a major problem in science recently. There is science and there is business — they are different and should be fundamentally driven by different goals: one, the pure and unadulterated desire for greater knowledge and the other, monetary gain. Branding science puts focus on making your research appealing, which is extremely limiting, and — dare I say? — corrupts the scientifi c process. There is a lot of fundamental research that needs to be conducted that is not ‘sexy’. Such ‘science branding’ has not yet affected the Chinese Academy of Sciences and for that I’m grateful.

- What’s your view on social media and science?

For example, the role of science blogs in critiquing published papers? Those who can, publish. Those who can’t, blog. I understand that blogs can be useful in affording the general public insights into current science, but it often seems those who criticize or spend large amounts of time blogging are also those who don’t generate much publications themselves. If there were any valid criticisms to be made, the correct venue for these comments would be in a similar, peer-reviewed and citable published form. The internet is unchecked and the public often forgets that. They forget or are unaware that a published paper passed rigorous review by experts, which carries more validity than the opinion of some disgruntled scientist or amateur on the internet. Thus, I find that criticism in social media is damaging to science, as it is to most aspects of our culture.

I completely agree with the first paragraph. At least for me, fundamental science is much more important than anything that you can think of (money, fame, 10000 followers etc.). People who know me in real life witness this pretty much every day. It's also clear that some people use social media to market their names and research. While I understand most of the reasons, I don't accept it.

When it comes to second paragraph, I can't say I totally agree. Yes, it's true there are a lot of people whose sole purpose is to criticize ANYONE and they usually do this as a group of like minded "scientists." But, if I were the scientist being criticized, I'd just ignore and let them talk. Would I ever answer? No. So, I think scientists shouldn't care what others say about them. After all, "What Do You Care What Other People Think?"

Finally, it's partly true that "Those who can, publish. Those who can’t, blog." I applaud Jingmai O’Connor for being honest. We need more people like her who can say what they think.

 

Book: Half-Life: The Divided Life of Bruno Pontecorvo, Physicist or Spy

I believe most of us who are not physicists or who are not much interested in physics have never heard of Bruno Pontecorvo's name. The moment I saw the title of the book, I fell in love with it and had this strong urge to read it. As a science books enthusiast, I consider myself a knowledgeable person when it comes to names of scientists and their accomplishments. But, there I was, standing in front of this book and had no idea who he was. 

Bruno Pontecorvo was an Italian physicist whose academic advisor was Enrico Fermi! Although he didn't excel in his informal examination with Enrico Fermi, he was accepted to join Fermi's team that was later known as Via Panisperna Boys as an experimental physicist. In fact, at the age of 21 he published his first paper with Fermi. Here he witnessed the first use of slow-neutron technique and became one of the names on the patent of this technology. Around this time, he became an active supporter of communism. The atmosphere being very dangerous for Jews, he fled Italy and joined Irene Curie and Frederic Joliot's research team. Later in 1940, he had to escape Europe to start his new job as an oil inspector in the US. He started to use neutrons to locate oil-rich terrains which would have made him a millionaire had he patented it as he confesses. In 1943, he joined the researchers at Chalk River to work on the nuclear projects there. By the end of the 2nd World War, he started to focus his research on neutrinos and how to capture them and moved to Britain in 1949 to work at Harwell. Here at Harwell, his ties to communism and previous suspicions about him caused a lot of trouble. Finally, in September 1950, Bruno and his family disappeared in Helsinki. It was 5 years later that the world heard of him. He was in Soviet Union working in Dubna. 

Frank Close did a wonderful job in combining Bruno Pontecorvo's science and his life. He gives enough information and background about the other names that are relevant to Bruno's story which is really helpful. We still don't know if he was a spy or not, but his contributions to physics is very clear. There have been a few Nobel Prizes in Physics  that he would have easily won. Unfortunately, being in Soviet Union, isolated and having limited access to modern equipment caused the Nobel committee not to recognize his work. This is not only a great life story, but also a really good popular science book where you can find technical but simple information about nuclear physics and the history of nuclear physics.

http://www.amazon.com/Half-Life-Divided-Bruno-Pontecorvo-Physicist/dp/0465069983

Book : Selections from The Principle of Relativity

Although I am familiar with Einstein's theories, I have never read anything written by him. Having finished Gravity, I thought it's time to read relativity from his own writings. I have more than one degree in STEM fields (fair to say I am good at math and physics), I don't have experience in reading physics papers though. Here is what I think about the book:

- I think the translation is not good. At first, I thought it's due to the language of physics and the way those papers are written, but later I realized that some sentences are indeed too long and missing pieces. I think it would have been much better if someone divided long sentences into small pieces while maintaining the meaning. I understand we can't really call that translation and the purpose of the book is not to reach everyone, but it would be easier to understand.

- To my surprise, I found Einstein's writings very clear. His thought experiments and the way he simplifies them are incredible. He is like a modern day Socrates building up his logic starting from the simplest assumptions and laws. He is very clear when he doesn't agree with another physicist or a theory. All the conclusions of his papers here are incredibly simple and easy to understand. He really avoids being too complicated as much as he can. 

- I am not studying physics and I don't have interest in using his equations to understand the universe around me, so I skimmed through his equations when he starts to derive the necessary but complicated equations for his work. But, still the general equations are not that complicated. 

- I loved the paper On the Influence of Gravitation on the Propagation of Light. Here how it starts:

In a contribution published four years ago* I tried to answer the question whether the propagation of light is influenced by gravitation. I return to this theme because my previous presentation of the subject does not satisfy me, but even more because I now see that one of the most important consequences of my former treatment is capable of being tested experimentally. For it follows from the theory to be presented here, that light-rays passing close to the sun are detected by its gravitational field so that the apparent angular distance between the sun and a visible fixed star near to it is increased by nearly a second of arc.

 I think it is one that I fully understood.

Overall, I think anyone who believes that he can understand university level physics and math should read this book. If you have time, there are tons of resources online where these papers are sort of "annotated" and are explained by other scientists. So, in a few weeks, you can easily fully grasp what a true genius Einstein was.  Like I said, my purpose was just to read his writings and his theories by his own words. I think I was able understand what he's trying to say. I am sure someone who is a physical chemist or physicist will fully grasp all the math behind the theories since he derives them one by one.

I don't think we'll ever have another Einstein.

Metal-based drugs that break the rules #chempaperaday 261

Since the accidental discovery of cisplatin's anticancer properties, people have tried to design platinum-based anticancer drugs. They did this mostly following the leading example of cisplation. Labile leaving groups, neutral compound, inert... More recently, people have been trying to break these "rules" and design and synthesize transition metal-anticancer complexes. Here in this article, you can read several examples of these compounds and the approach on their synthesis and purposes.

http://pubs.rsc.org/en/content/articlelanding/2016/dt/c5dt03919c#!divAbstract

Friedrich Miescher and the discovery of DNA #chempaperaday 260

I have to admit that I didn't know much about Miescher other than that he's the first one to isolate DNA. After reading this article, I am embarrassed. Now I believe that he's one of the most underrated and ignored scientists ever!

Luckily, this is an open access paper and it reads like a fascinating story. His father and uncle were famous professors and Misescher started his medical training by their influence. Later, he focused on research which was his true passion. You can read how he first isolated DNA (he termed "nuclein") and his first two protocols for the isolation. But, what really amazed me is that he did all these without pretty much any modern instrument. Nevertheless, he was such a good experimenter that he calculated the P2O5 proportion as 22.5% (today we know it's 22.9%) Unbelievable! He had many more accurate predictions which people didn't realize until mid 40's. Too bad he died at the age of 51. 

There is also a very nice timeline of DNA.

1865: Gregor Mendel discovers through breeding experiments with peas that traits are inherited based on specific laws (later to be termed “Mendel's laws”).

1866: Ernst Haeckel proposes that the nucleus contains the factors responsible for the transmission of hereditary traits.

1869: Friedrich Miescher isolates DNA for the first time.

1871: The first publications describing DNA (“nuclein”) by Friedrich Miescher, Felix Hoppe-Seyler, and P. Plósz are printed.

1882: Walther Flemming describes chromosomes and examines their behavior during cell division.

1884–1885: Oscar Hertwig, Albrecht von Kölliker, Eduard Strasburger, and August Weismann independently provide evidence that the cell's nucleus contains the basis for inheritance.

1889: Richard Altmann renames “nuclein” to “nucleic acid.”

1900: Carl Correns, Hugo de Vries, and Erich von Tschermak rediscover Mendel's Laws.

1902: Theodor Boveri and Walter Sutton postulate that the heredity units (called “genes” as of 1909) are located on chromosomes.

1902–1909: Archibald Garrod proposes that genetic defects result in the loss of enzymes and hereditary metabolic diseases.

1909: Wilhelm Johannsen uses the word “gene” to describe units of heredity.

1910: Thomas Hunt Morgan uses fruit flies (Drosophila) as a model to study heredity and finds the first mutant (white) with white eyes.

1913: Alfred Sturtevant and Thomas Hunt Morgan produce the first genetic linkage map (for the fruit fly Drosophila).

1928: Frederick Griffith postulates that a “transforming principle” permits properties from one type of bacteria (heat-inactivated virulent Streptococcus pneumoniae) to be transferred to another (live nonvirulent Streptococcus pneumoniae).

1929: Phoebus Levene identifies the building blocks of DNA, including the four bases adenine (A), cytosine (C), guanine (G), and thymine (T).

1941: George Beadle and Edward Tatum demonstrate that every gene is responsible for the production of an enzyme.

1944: Oswald T. Avery, Colin MacLeod, and Maclyn McCarty demonstrate that Griffith's “transforming principle” is not a protein, but rather DNA, suggesting that DNA may function as the genetic material.

1949: Colette and Roger Vendrely and André Boivin discover that the nuclei of germ cells contain half the amount of DNA that is found in somatic cells. This parallels the reduction in the number of chromosomes during gametogenesis and provides further evidence for the fact that DNA is the genetic material.

1949–1950: Erwin Chargaff finds that the DNA base composition varies between species but determines that within a species the bases in DNA are always present in fixed ratios: the same number of A's as T's and the same number of C's as G's.

1952: Alfred Hershey and Martha Chase use viruses (bacteriophage T2) to confirm DNA as the genetic material by demonstrating that during infection viral DNA enters the bacteria while the viral proteins do not and that this DNA can be found in progeny virus particles.

1953: Rosalind Franklin and Maurice Wilkins use X-ray analyses to demonstrate that DNA has a regularly repeating helical structure.

1953: James Watson and Francis Crick discover the molecular structure of DNA: a double helix in which A always pairs with T, and C always with G.

1956: Arthur Kornberg discovers DNA polymerase, an enzyme that replicates DNA.

1957: Francis Crick proposes the “central dogma” (information in the DNA is translated into proteins through RNA) and speculates that three bases in the DNA always specify one amino acid in a protein.

1958: Matthew Meselson and Franklin Stahl describe how DNA replicates (semiconservative replication).

1961–1966: Robert W. Holley, Har Gobind Khorana, Heinrich Matthaei, Marshall W. Nirenberg, and colleagues crack the genetic code.

1968–1970: Werner Arber, Hamilton Smith, and Daniel Nathans use restriction enzymes to cut DNA in specific places for the first time.

1972: Paul Berg uses restriction enzymes to create the first piece of recombinant DNA.

1977: Frederick Sanger, Allan Maxam, and Walter Gilbert develop methods to sequence DNA.

1982: The first drug (human insulin), based on recombinant DNA, appears on the market.

1983: Kary Mullis invents PCR as a method for amplifying DNA in vitro.

1990: Sequencing of the human genome begins.

1995: First complete sequence of the genome of a free-living organism (the bacterium Haemophilus influenzae) is published.

1996: The complete genome sequence of the first eukaryotic organism—the yeast S. cerevisiae—is published.

1998: Complete genome sequence of the first multicellular organism—the nematode worm Caenorhabditis elegans—is published.

1999: Sequence of the first human chromosome (22) is published.

2000: The complete sequences of the genomes of the fruit fly Drosophila and the first plant—Arabidopsis—are published.

2001: The complete sequence of the human genome is published.

2002: The complete genome sequence of the first mammalian model organism—the mouse—is published.

What a great man, scientist. And here I am, with all the instruments I have, I still complain that I can't isolate a certain compound. From now on I will not complain. The more challenging it gets, the more aggressive I'll pursue that goal!

http://www.sciencedirect.com/science/article/pii/S0012160604008231

Manganese Electrocatalysts with Bulky Bipyridine Ligands #chempaperaday 259

This is a really cool and interesting paper where Mg2+ ions are used with the Mn catalysts. The authors say it's a "rare" example. I wish they cited the other examples. Anyway,  I think it's an amazing paper with beautiful looking data. And if you like coordination chemistry, I am sure you'll like the catalysts themselves too. I don't know much about electrochemistry, but the results are still impressive to me.

http://pubs.acs.org/doi/abs/10.1021/jacs.5b12215

The Heroes of CRISPR #chempaperaday 258

By far the best article to explain what CRISPR is and the history of it. Most people (even scientists I know) mention CRISPR with the names Doudna-Carpentier-Zhang. I've tried to read about CRISPR on wikipedia and I also read some review articles to really see how it was discovered. But, as you'll also confirm it is really hard to find a source that explains everything in chronological order and in simple terms. I know some biology but I am not molecular biologist. When an article goes in too many details, I get lost. So, this article REALLY helped me to read the history of it. It is unbelievable how many early researchers' papers got rejected even without reviews! Tells a lot about the journal/author/lab names. Really sad! But, it looks like it's how publishing works. All those early researchers I think deserve more credit than the three I mentioned above. They spent years to understand what these repeats are for and the mechanism that goes with the process. 

It is a really nice read and ANYONE can understand this article.

http://www.cell.com/cell/pdf/S0092-8674%2815%2901705-5.pdf