Tuesday, April 28, 2015

Approaches to the design of catalytic metallodrugs #chempaper 213

Well, we can do catalysis using transition metals. Can we do the same in biological systems? Moreover, can we do biochemical transformations? The answer is yes, we can and here are a few examples of these remarkable processes.

In this brief review, you can read several examples of metal catalyzed cross coupling reactions for fluorescent labelling, deprotection of azides/carbamates, activation of metallodrugs, cleavage of peptides, nucleic acid chains and proteins (HIV1, RNA etc.), using NADH for transfer hydrogenation and many more transformations that are done in biochemical environment. Some of them are their infancy, but there are some in Phase II/III stages and there is even one approved in Russia.

Monday, April 27, 2015

Is there a common chemical model for life in the universe? #chempaper 212

Fantastic article on what life is and whether we can find it elsewhere. Biology and life itself drives me crazy and I want to see the discovery of other or similar life forms before I die. The authors ask all the questions you could possibly ask. If you are one of those who ask "Why?" a lot, this article is definitely for you.


Why 20 amino acids?
Why 4 DNA bases?
Why carbon?
Why water?
Could any other solvent support life?
and tens of other questions are really well explained here. The references are so great that I will probably end up reading 50 of them.

Sunday, April 26, 2015

Design, synthesis, and carbon-heteroatom coupling reactions of organometallic nickel(IV) complexes #chempaper 211

This is the second octahedral organometallic nickel (IV) complex and also shows a unique reactivity. These made it into Science I guess. When I say I am not much impressed by the paper, people tell me that I am absolutely wrong. But, I still think the same. It's cool, what it does is very cool, I respect the way to make it and isolate it, but I think there will be many more interesting Ni(IV) compounds and unfortunately I think many of them won't be able to make it to Science.


Rhodium-Catalyzed Hydrosilylation of Ketones: Catalyst Development and Mechanistic Insights #chempaperaday 210

It's a very nice review on hydrosilylation with rhodium catalysts. Not the most recent, but a very good one.

There are very active and selective Rh catalysts out there, but the price of rhodium makes it less attractive. So, there is huge effort on developing catalysts with cheaper first row transition metals. Nevertheless, mechanisms of Rh catalyzed reactions are pretty well understood for now and it's still an active research area.


Thursday, April 23, 2015

Book: The Kaiser's Chemists: Science and Modernization in Imperial Germany

This book is a great source on the history of chemistry and its relation with politics, governments and of course war. 

By the end of the 19th century, some German chemists (Emil Fischer -"a pillar of militarized science" in particular) started to think that they were losing their position in chemistry (especially in inorganic chemistry) to the US. "We must do more for inorganic and general chemistry again, if we are not to be put to shame by other countries."
Fischer and several other chemists decided to convince the Kaiser to fund chemistry and open new labs. What they had in mind was a large research facility with the most modern equipment. So, it took years and a lot of PR to convince companies and the Kaiser himself to open these research centers. Not surprisingly for those years, about half of the funding came from Jewish businessmen (you can read the reasons in the book). These centers, in turn, brought much success to Germany and tens of Nobel Prize winners. 

The best part of the book in my opinion is that it allows you read the discussions among academicians and politicians regarding the importance of funding, research ideas and commercial applications of the products. Just like today, many chemists believed that chemistry was no longer a career or how little chemists were respected. There were also fights among several professors on why there were few positions (or too many chemists). On the other hand, there were chemists telling that there were too many professors at upper ranks. Professors complaining about teaching duties... Basically, everything was exactly the same as today.

There are also so many details that I didn't know about such as the rivalry between Nernst and Haber, Willstatter's research interest in photosynthesis in the living leaf, Einstein's pacifist letter with only 4 signatures and Fischer's wish for Haber's tests "failure from the bottom of my patriotic heart"

Some interesting quotes:

"Science did not escape the rise of nationalism but adapted to it.

[Ostwald] it was not frequently claimed that I was no chemist, because I never produced a new substance.

Big science, like big industry, needs operating capital.

Standstill is retreat (Duisberg).

As an Austrian women, a Jew and a physicist, Meitner's presence meant little to the German chemists....with the nonposition of unsalaried "guest".

[A university professor] is freer, because he can replace many assistants by students and doctoral candidates.

[Harnack] our enemies...brought German science and military strength as close together as possible.

[Liebknecht] science and research in uniform have hardly ever done good.

...the war converted him [Ostwald] virtually overnight, to an ultranationalist. "

Sunday, April 5, 2015

Pauling's Left-Handed alpha-Helix #chempaperaday 209

Left-handed alpha-helices are not common. In fact, I was able to find only one example with my limited search attempts although I am sure there are many more. There are stereochemical issues, bond distance and dihedral angle restrictions if nature or  you want to make one of them. So, when I first saw the title, I did not want to believe that Pauling proposed a left-handed alpha-helix. I thought he just made a mistake in one of his books or papers. If you read the paper, you will see that this is not the case. For some reason unknown to us, he drew this helix. As the paper explains, in fact he made an arbitrary assignment to R groups when he first reported "the structure of proteins."

But, as the author explains in detail, he should have known the absolute configuration of the amino acids. In fact, his colleagues at his own department were doing research on the subject. So, he should definitely have known much more about his "incorrect" assignment. You can read the article and learn more about the issue. My own understanding is that he was not in close communication with his faculty members in those years due to the political troubles he had had. Maybe the people who really knew the absolute configuration did not correct him on purpose, or he did not want to be corrected by one of those people who were not on his side when he needed support. But, I don't think he was simply not "interested in the problem of absolute configuration." I think this is contrary what we know about his scientific curiosity and genius.

The author is Jack D. Dunitz who is a giant in his field and you may know his name if you can remember Burgi-Dunitz angle.

Elongated dihydrogen complexes: what remains of the H–H Bond? #chempaperaday 208

Most transition metal dihydrogen complexes have an H-H distance less than 1 Angstrom. The rest of the complexes have longer H-H bond distances making them what is called "elongated dihydrogen" complexes. Of course if the distance is larger than 1.5 they become dihydride compounds.

In this short review, there is a lot and much useful information for those who want to learn more about these interesting complexes. Because it is difficult to resolve the crystal structures containing these ligands, there are a few methods to characterize them. Probably the simplest method is to use HD and measure the coupling constant and then plug it in in this formula :

There are ten "representative" complexes in the article that really help you to get a better understanding. I like the idea of listing these complexes and giving details about them. I think more authors should try this type of writing. Most review articles only cite other papers and avoid giving detailed information which makes following the paper really hard in some cases.

Saturday, April 4, 2015

At Least 60 Years of Ferrocene: The Discovery and Rediscovery of the Sandwich Complexes #chempaperaday 207

This is probably one of the most interesting and surprising articles I have read. 

I guess all inorganic/organometallic chemists know (I hope) the story of the discovery of ferrocene and other sandwich complexes. It all starts with Pauson and Kealy's Nature papers on the discovery of an unusually stable compound ("What was this remarkable substance we had made?") and goes on. I will not go into the story. If you want to learn, you should read this paper and many other historical papers on these compounds. Later, it turns out that in fact they were not the first people to discover this compound. Many other people had already seen this complex but they simply did not report it. The compound gets attention from several chemists including Woodward, Fischer and Wilkinson. In fact, the name ferrocene was given by Woodward. Soon, the competition between Fischer and Wilkinson started. They literally divided "the periodic table between them".

This is an incredibly well written story. The most interesting two things for me are the comments of a reviewer and Woodward's comments on the Nobel Prize in Chemistry.

First, the referee writes to Woodward "We have dispatched your communication to the printer but I cannot help feeling that you have been at the hashish again."

Secondly, Woodwards writes to the committee on the Nobel prize saying "...I am sure-committed a grave injustice...Both of these concepts were simply, completely, and entirely mine, and mine alone." wow!

"Modeling the Active Site of [NiFe] Hydrogenases..." #chempaperaday 206

I found this paper very good both in the quality of research and explaining simple but important details about hydrogenases. Contrary what many people think there is not one type of hydrogenase. There is a recent and very good review here if you are interested. I will read it soon,

Michele Peyrone, Discoverer of Cisplatin #chempaperaday 205

Cisplatin is a very effective anticancer drug especially against testicular cancer. It is also probably one of the most important metal complexes that opened a new research area for developing anticancer drugs. Its biological activity was discovered accidentally by Barnett Rosenberg and colleagues and it was approved by FDA in a very short time compared to any other drugs. 

Anytime you read a biochemistry or bioinorganic chemistry paper about metal anticancer complexes (covalent ones especially), you can read a very similar introduction. But, some of them also mention that the complex was synthesized almost 100 years prior to its "fame". Cisplatin was first synthesized by Michele Peyrone in 1844. Knowing nothing about isomerism of course, Peyrone described the physical properties of the compound and hypothesized its forming. It was then named as Peyrone's  Chloride.  I found it very interesting that Peyrone worked under Justus von Liebig. Later, Peyrone focused on agricultural chemistry and did not pursue his studies on platinum compounds.

The article is written by four authors and the name George B. Kauffman caught my attention of course. I know his writings very well and try to read as many as possible

It was good to know Michele Peyrone closer and I suggest you do the same.

Thursday, April 2, 2015

Book: "Linus Pauling and the Chemistry of Life"

I said it before and I will say it again. Linus Pauling deserved to win 3 unshared Nobel Prices in chemistry. In any field of chemistry, you can see his impact. He's always there.

This book is probably the best biography of Linus Pauling. I opened the book a very late time at night and I just couldn't stop reading it until I finished and I wish it had not finished. Such an amazing storytelling. I knew a lot about his life even before reading the book, but I still learned a lot. I knew he had trouble with government but I did not know that FBI investigated him for 24 years and some of the funding agencies cut his research funding. He had really hard time finding a place to work! What a shame. How unfair! 

There is no other chemist that revolutionized chemistry and medicine as much as he did. He was a true genius and it's a shame that for decades he was alienated by his colleagues and his government.

Wednesday, April 1, 2015

Book: "The Devil's Doctor"

Since I discovered Philip Ball and his writings, I have been reading everything he produces. In my opinion, he is by far the best science writer. I am also interested in reading everything about Paracelsus since I consider himself one of my heroes in science and medicine no matter what people think about him. I think he played a very important role in modernization of chemistry and medicine. 

If you think this book is an ordinary biography, you are mistaken. The book is really well written with the most interesting stories and endless journeys of Paracelsus. You will not only read his life, his work and trips; but also the political and religious environment of his age. 

If you ever read anything about Paracelsus, you probably know that he traveled almost anywhere accessible in 16th century to learn how different people fight the diseases. He was outspoken, and he had "extreme" ideas and sometimes practices that gave him trouble. To him, schools were not really the only places that you can learn a profession: "At all the German schools, you cannot learn as much as the Frankfurt fair." Traveling was so important for him that once he said "If a man wishes to recognize many diseases, let him travel." 

I think the book is a fascinating work on Paracelsus. Unlike several other books, the book does not have a fixed idea on Paracelsus' character or whether we should take him seriously or not. This makes the book even more special by allowing us to have our own opinion.

I strongly recommend this book for science, medicine, philosophy, philosophy of science and chemistry enthusiasts. My personal opinion is that Paracelsus was a great man and scientist and we owe him a lot. Since I first heard of his name when I was a little boy, I always felt very close to him. What I like him the most as Philip Ball says "always he was no one's man but his own."