Challenges and Opportunities in the Development of Organometallic Anticancer Drugs #chempaperaday 193

A very short review of organometallic anticancer compounds as "drugs" ending with possible 8 opportunities for chemists to design these types of compounds.

http://pubs.acs.org/doi/pdf/10.1021/om300373t

One Hundred Years of the Fritz Haber Institute #chempaperaday 192

Fritz Haber Institute is one of the "sub" institutes of Max Planck Institute. Unless you are interested what they do, you probably have not heard of the institute. Since, I follow some of their research areas, I can say I know a some about the institute and in fact it would be an honor for me to work there one day in the future.

So I was really happy when I came across this paper about a month ago. It's a short history of the institute and the research within covering one hundred years. I am glad I read it because I was able to learn much more than I know about FHI. I did not know FHI had seven Nobel laureates for example.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201104792/abstract

                                                                   Photo: Wikipedia

If you read the paper, you will learn how much the institute contributed to modern science especially in surface chemistry, heterogeneous catalysis and electron microscopy. I would like to highlight a few titles that were also related to FHI: gas masks, methane detector, allotropes of hydrogen, symmetry. 

The fields of research explained by the paper are:

Gas-Phase Kinetics and Dynamics

Methane Detector

Haber-Born Cycle

Chemiluminescence

Combustion

Sttatistical Mechanics

The Franck-Hertz and the Compton Effects

Dispersion

Theoretical Chemistry

Molecular Beams

Physisorption

Colloid Chemistry

Electron Microscopy

Surface Science

[The] science research project of today is the temporary culmination of a very long, hard- fought struggle by a largely invisible community of our ancestors. Each of us may be standing on the shoulders of giants; more often we stand on the graves of our predecessors.

"In the words of the historian Fritz Stern, Haber' s Institute during the First World War became “ kind of forerunner of the Manhattan Project."

Gallium-Iron multiple bond controversy #chempaperaday 189-191

I have three papers starting with a report claiming that there is evidence for a Ga-Fe triple bond and they named it "ferrogallyne."

http://pubs.acs.org/doi/abs/10.1021/om970530c

As you can see the evidence for this so-called multiple bond was not so convincing. So, being an expert in multiple bonds, F.A. Cotton wrote his comments and concerns about this assignment. He explained his reasoning and suggested that there is also a dative bond between Ga and Fe.

http://pubs.acs.org/doi/abs/10.1021/om970971w

There was no reply from the original authors. So, this is unfortunate. I was able to find a computational paper on the issue. But, it's not the best paper to read on the subject. The authors simply say that the triple bond is a "pseudo-conflict" in this case because our bonding model is not "appropriate." Personally, I agree with Cotton and I think there should only be a Ga->Fe bond.

Lewis Acidity of Organofluorophosphonium Salts #chempaperaday 187-188

The paper I read was "Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor that was published in Science. The second one is the "perspective" by F.Gabbai in the same issue. 

Caputo, C. B.; Hounjet, L. J.; Dobrovetsky, R.; Stephan, D. W., Lewis Acidity of Organofluorophosphonium Salts: Hydrodefluorination by a Saturated Acceptor. Science 2013, 341 (6152), 1374-1377.

Gabbaï, F. P., Lewis Acids with a Difference. Science 2013, 341 (6152), 1348-1349.

I pretty much knew nothing about hydrodefluorination until I read these papers. Now I know some. Really difficult research but it's not very popular yet. So, there is a lot of opportunities in this area of research.

Whittlesey, M. K.; Peris, E., Catalytic Hydrodefluorination with Late Transition Metal Complexes. ACS Catalysis 2014, 4 (9), 3152-3159

"Synthesis, Characterization, and Structures of a Persistent Aniline Radical Cation" and the controversy #chempaperaday 183-186

The recent controversy and discussion starts with the publication of the report of a stabilized aninile radical cation.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201205478/suppinfo

Here the authors claim that they were able to stabilize the radical cation and report x-ray structures, electrochemical studies and some EPR data.

Shortly after this paper, two comments appear:

Comment on “Synthesis, Characterization, and Structures of Persistent Aniline Radical Cation”: It Is a Protonated Aniline and Not an Aniline Radical Cation

http://onlinelibrary.wiley.com/doi/10.1002/anie.201305293/suppinfo 

and 

Comment on “Synthesis, Characterization, and Structures of a Persistent Aniline Radical Cation”: A New Interpretation Is Necessary

http://onlinelibrary.wiley.com/doi/10.1002/anie.201303991/suppinfo 

The commenters try to replicate the experiments and they basically say that it is not an aniline radical. They have some detailed studies and explanations.

Finally, the original authors publish a reply to those two comments here:

Reply to Comments on “Synthesis, Characterization, and Structures of Persistent Aniline Radical Cation”

http://onlinelibrary.wiley.com/doi/10.1002/anie.201308539/abstract;jsessionid=5279D35F4E3D1A886730106324AE798C.f01t03

The problem with the "reply" is that they accept some of their "mistakes" and claim that they obtained the aniline radical cation. But, they can't really clarify some of the other concerns that the commenters pointed out.

Really interesting read.

Book: Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves

George Church is a great mind and scientist. I had the chance to listen to his talk in Museum of Science last year. So, when I saw the book by him, I didn't even hesitate one second. I knew it would be a great read. After reading it, I can say I was absolutely right. Whether you like biology or not, whether you know some biology or not, you should read the book. It is not only a book about synthetic biology and the future of it, it is also about humanity, the fate of humans and our society.

"Imagine a future in which human beings have become immune to all viruses, in which bacteria can custom-produce everyday items, like a drinking cup, or generate enough electricity to end oil dependency. Building a house would entail no more work than planting a seed in the ground. These scenarios may seem far-fetched, but pioneering geneticist George Church and science writer Ed Regis show that synthetic biology is bringing us ever closer to making such visions a reality. In Regenesis, Church and Regis explore the possibilities—and perils—of the emerging field of synthetic biology. Synthetic biology, in which living organisms are selectively altered by modifying substantial portions of their genomes, allows for the creation of entirely new species of organisms. Until now, nature has been the exclusive arbiter of life, death, and evolution; with synthetic biology, we now have the potential to write our own biological future. Indeed, as Church and Regis show, it even enables us to revisit crucial points in the evolution of life and, through synthetic biological techniques, choose different paths from those nature originally took. Such exploits will involve far more than just microbial tinkering. Full-blown genomic engineering will make possible incredible feats, from resurrecting woolly mammoths and other extinct organisms to creating mirror life forms with a molecular structure the opposite of our own. These technologies—far from the out-of-control nightmare depicted in science fiction—have the power to improve human and animal health, increase our intelligence, enhance our memory, and even extend our life span. A breathtaking look at the potential of this world-changing technology, Regenesis is nothing less than a guide to the future of life."

The above paragraph is straight from the Amazon webpage for the book. I had to quote it because I can't write anything better than that. It's an easy to read book so I am pretty sure anyone who has 3-4 hours on a weekend will easily finish reading it. You will not only learn how synthetic biology can change our future but also how important it has become in our lives without even realizing it. Moreover, if you want to be an entrepreneur in biotech there are tens of examples of them; how they were founded, how and why they succeeded (or didn't), the challenges and even future directions.

Before you look up for the definition of synthetic biology, let's see how George Church describes it:

"the science of selectively altering the genes of organisms to make them do things that they wouldn;t do in their original, natural, untouched state."

As usual, I have quotes :

"Creating a mirror world might give us a fresh lease on life, one free of disease and unwanted agricultural pest species."

"...species that are lowest in diversity are most vulnerable to extinction."

"Give me a selection, and I will change the world."

"Multicellularity tends to come with a hard consequence-you give up your immortality."

"...just as individuals respond differently to drugs and to pathogens, they also respond differently to information."

"What should we do? Doing nothing, or doing what is traditional or natural, is not even close to a recipe for survival. If we choose tomorrow to behave in a way that our primitive ancestors did, nearly all of our 7 billion humans will die."

Alfred Werner's seminal 1910 paper on polynuclear cobalt complexes: What have we learnt since then?

Alfred Werner is one of my heroes in chemistry. He's probably in top 3 with Linus Pauling and Fritz Haber. I wrote posts about him before. Also here are two links about the controversy between him and Jorgensen:

S. M. Jørgensen and His Controversy with A. Werner: A Reconsideration 

Sophus Mads Jørgensen and the Werner-Jørgensen Controversy

But, he has some role on almost anything I write about inorganic chemistry since he is the founder of coordination chemistry and probably the most important chemist who showed people the importance and power of inorganic chemistry. What he did in his limited time (he died at the age of 53) and with his limited equipment is simply incredible. He left us hundreds of pages of publications, books and his legend. 

Karl Wieghardt is among my scientific heroes and as I said before I hope I can work for him one day. Here is an interview with him that I posted before. So, I am extremely happy to hear him giving a talk about Alfred Werner. I will not spoil it for you, because I really want you to watch/listen to this presentation by him about Alfred Werner. Once again, I hope you will realize and share my thoughts about Alfred Werner. Because, as Werner's life, the presentation is also full of surprises. I am pretty sure you will learn many things about Werner that you haven't heard so far. I hope you enjoy it.

http://presentations.acs.org/common/media-player.aspx/Fall2013/INOR/INOR004/17075

The Principle of Membrane Fusion in the Cell (Nobel Lecture) #chempaperaday 182

I try to read as many Nobel lectures as possible. You can often find really important pieces in those successful scientists' life and career that might help you figure out a problem in your research or a way to approach the problem.

This Nobel lecture on membrane fusion by J.E. Rothman is among the best. Just like many other Nobel laureates, he also has an interesting and diverse background that helped him throughout his career.

According to him, "the key elements for breakthrough" are:

-an ideal working environment

-The choice of the right problem at the right time

-A unique way of approaching the problem

         -hard work and persistence to develop a method that works in the wake of many painful failures

-the right partner to attack the problem

-stable research funding

"there is no process in biology that, at its very core, is not physical-chemical

in nature. As the direct consequence, we can expect that, in due course, all of

life—even human thought and emotion—will be understood as emergent from

physics and we will understand ourselves in health and in disease as complex,

organically composed self-determining machines. This is a perspective that may

frighten some, but it should not because it offers our species the best hope for

the long term."

 "How Does a Physicist Approach the World (including the Biological World)?

-Seeks universal laws to explain all related processes on a common basis

-Formulates the simplest hypothesis to explain the facts

The simplest hypothesis:

-Intrinsic chemical specificity governs transport, not intracellular anatomy"

Here is the lecture slides :

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/rothman-lecture-slides.pdf

Here is where I read the lecture:

onlinelibrary.wiley.com/doi/10.1002/anie.201402380/abstract

Also here:

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/rothman-lecture.pdf

Fritz Haber: The Damned Scientist - #chempaperaday 181

I couldn't help reading another article on Fritz Haber today.

 

Like every persont, he had a personal life and he made choices. All I am interested in him is his science and I admire his science.

Fritz Haber: Flawed Greatness of Person and Country #chempaperaday 180

This is the second article I have read (at least after I started to blog) on Fritz Haber. The first one, in case you are interested is here. This one is a more biographical article written by Fritz Haber's godchild Fritz Stern for the 100th year of Fritz Haber Institute. If you are interested in history of science, I think you should definitely read it.

"In our world so fond of denigration, of alleged honesty honed by political correctness, Haber is often remembered as a vain chauvinist."

"To understand Haber is to understand Germany and to some extent the opposite applies as well. They illuminate each other."

"He was a German patriot committed to an international enterprise, science."

"Haber flourished in Wilhemine Germany; the Kaiser set the tone and Haber played to the tune."

"The defense of scientific research as fundamental to national defense was an argument that Haber was to use throughout his career."

"I regret that we live in an age of denigration, and I want to mention an American instance of blemished greatness now being distorted in a faintly analogous process."

Transition metals in plant photosynthesis - #chempaperaday 179

This is a minireview about the roles of Cu, Fe, Mn and Zn in plant photosynthesis and finally there is a very short part on artificial leaves with Ni. The role of the transition metals in biology amazes me. They are so important that deficiency or higher concentrations of these metal ions have detrimental effects on the plants' or other living organisms' lives. Sometimes I think that some metal ions have very similar ionic radii and in fact it should not be a huge problem to have one instead of another. But, when you look at the biology you see only one ion instead of the other. How is this regulated? What brings those metal ions and places them in those proteins or organelles? Yes, there are chaperones but what is the source of this incredibly high selectivity and how are they transported? I hope one day we will learn.

http://pubs.rsc.org/en/content/articlelanding/2013/mt/c3mt00086a#!divAbstract

Book: The World's Greatest Fix by G.J.Leigh

This was the last book I read in 2014 and in fact I finished reading it on the 30th.

I was surprised that the first half of the book was about the history of fertilizers and agriculture (I should have understood it from the title!). Then comes the second part about the discovery of nitrogen and the historical progress towards Haber-Bosch process. These chapters were full of inorganic an industrial chemistry with several journal articles that I would love to read as soon as possible. I had always thought of Haber's method for nitrogen fixation as a more serendipitous discovery instead of a scientific research. I could not be more wrong. Also, Bosch's coworker Alois Mittasch tested "2500 different catalysts in 6500 runs within about one year." So much of the process (or reactions) were already studied in detail and there were other methods in use for nitrogen fixation. But, Fritz Haber (and Bosch) was the only one who made it work more efficiently and turned it into an industrial process. Final chapter is about nitrate and nitrite for those who are concerned of their affects on health and environment. Again, here you find a lot of peer reviewed journal articles as references. I think this was one of the best science books (chemistry in particular) I have ever read. Here are some quotes from the book:

"Alchemists, no less than modern scientists, were keen to find sponsors."

"No scientist ever makes a fundamental discovery that owes absolutely nothing to his predecessors."

"Today one can no longer whisper the magic words "nitrogen fixation" to granting bodies and expect to be funded."

"...%40 of all people alive today are dependent upon Haber-Bosch nitrogen...."

"There is a need for people to be much more educated scientifically, so they can make their own informed judgements."

"scientists...like the alchemists, so many employed by modern equivalents of rich princes hoping to find the philosopher's stone."

"Coping with Fritz Haber's Somber Literary Shadow" #chempaperaday 179

This is a beautiful article on Fritz Haber and how he was represented in several forms of art.

"Fritz Haber is often this scapegoat...Most of us are also teachers. We have to do better than the usual, traditional technical presentation of the ammonia synthesis, invoking it as a fine illustration of Le Chatelier's Principle. We have to talk also about Haber, the historical figure and the person. His choices and agony are a part of us."

http://onlinelibrary.wiley.com/doi/10.1002/1521-3773%2820011217%2940:24%3C4599::AID-ANIE4599%3E3.0.CO;2-K/abstract

"Valence Bond Theory in Coordination Chemistry" #chempaperaday 178

This is a very short paper by Linus Pauling. Apparently, he read an article where the author said that valence bond theory was not as popular and useful as it was. Obviously, the response came from Pauling and his response in fact was very short:

"I do not agree with this opinion."

The rest of the article explains how valence bond theory is still can be used in coordination compounds.

The article was published in Journal of Chemical Education, but here you can read it as pdf for free.

http://depa.fquim.unam.mx/amyd/archivero/VBPAULING_26400.pdf

Book: A Troublesome Inheritance

A few months ago (or maybe it was summer), I saw many people arguing about this book whether the author Nicholas Wade expressed "racist" ideas and whether the book had any "value" etc. I hate debates on what people call "controversial" topics. In my world, there is nothing controversial. You can say what you want. I respect everyone's ideas and even "insults." Also I had enough reasons to think that the book was worth reading. First, I read this post and then I saw several people's and "scientists" ' anger towards the author and his post. 

So, I bought the book and read it. 

I found the book really well written and clear. There are several parts that I do not agree with the author. But, there is no need to try to insult the author or the book. Moreover, there is no need to try to suppress others' ideas. Censor has no place in this century and in this country. It absolutely has no place in science. So, if you don't agree with him, you can try to write a better one and disprove what he said. It must be very simple if you are an expert in your field. This is where the problem stems from. Being a "science blogger" does not give you any credibility or expertise in a specific field of science. I saw people saying the he is not an expert so he is not eligible to write  book like this. Well, hello everyone can write anything as they want just like you write blogposts on topics that you have no understanding of. 

I saw a group of scientists wrote a letter saying "We are in full agreement that there is no support from the field of population genetics for Wade’s conjectures." This is the best way at least to tell public that there are flaws in the book. A better one would be to write a better book defending your position. But, I guess not many people will do that since it requires writing more than a few hundred sentences. 

As far as I know, Wade gave an answer and said that he had asked for feedback but had never gotten any or something along these lines (I don't remember where I read it). So, it looks like the debate will go on. Maybe he will write another book. We will see.

Anyway, I think the book is worth reading. Believe it or not, the whole book is not about race and genetics. 

A few quotes worth noting (not associated with race debate) :

"researchers do not act independently but rather as communities of scholars who constantly check and approve one another's work."

 "[Paul Samuelson] Knowledge advances, funeral by funeral."

"Science is about what is, not what ought to be."

Book : Memoirs by Edward Teller

No matter what people say about him, Edward Teller is one of my science heroes. I don't care about his personal life or some of his "controversial" ideas. I care about his approach to science and research. He was a great mind and truly a genius.

His Memoirs is a really long (602 pages) but a fun to read autobiography. The story of his life is also the story of science (nuclear physics/chemistry) that covers almost a century. I think you should read the book even though you don't like anything about him. There are tens of stories, memories, people that you will find interesting to learn about.

I really enjoyed his Memoirs and took some notes. I will quote a few of them here (as always I do not agree with him or others on everything they said):

"Before I was ten, I understood that in the United States foreigners are not foreign."

"Nationalism has little to contribute today except further suffering."

"Ignore teasing."

"...before the 1880s, science played almost no role in the advances of technology...Chemistry was the first science to undergo a merger with technology, and the first technology affected was dyemaking."

"He [Heisenberg] complained that physics had ceased to develop; there was hardly anything interesting left to do."

"Bohr:Where we find a paradox, we find something of real interest."

"Bohr said that to be properly understood, one should not lecture in his native tongue."

"The lesson is that the correct theory applied to the wrong data is better than no theory applied to correct measurements."

"[Bohr] Opennes is the basic condition necessary for science."

" Johnny [von Neumann] was the Euclid of quantum mechanics."

 "The scientist is not responsible for the laws of nature. It is his job to find out how these laws operate...Hydrogen bombs will not produce themselves."

"Science historically had moved forward because of openness."

"I find the idea of civil disobedience in a democracy wrong."

"Fermi and I both lacked formal religious beliefs"

"I believe that if a mentally superhuman race ever develops, its members will resemble Johnny von Neumann."

"I had begun teaching Paul[his son] relativity theory when he was five or six...he understood the theory of relativity by the time he was twelve."

[about Plato's Republic]" I was shocked that a book advocating a centralized government administered from above, much on the lines of totalitarianism, was so highly recommended to young people." 

Epoxidation #chempaperaday 167-177

Sharpless, Jacobsen, Shi

Comp.Org.Syn. 1991, 389
JOC 1986, 1922
JACS 1991, 113
JACS 1991, 106
JACS 1990, 2801
JACS 1991, 7063
TL 1990, 7345
Science 1997, 936
JACS 2002, 1307
JACS 1996, 9806
JACS 1997, 11224

Dihydroxylation #chempaperaday 159-166

Sharpless, Upjohn

JACS 1976, 1986
TL 1976, 1973
JACS 1980, 4263
JACS 1988, 10986
JACS 1989, 1123
JOC 1976, 766
TL 1990, 2999
JOC 1992, 2768

Hydrogenation #chempaperaday 144-158

Selected examples and mechanisms below:

Wilkinson, Crabtree, Knowles

JCS CC 1973, 629
JCS CC 1968, 1445
JACS 1977, 5946
JACS 1977, 2576
Science 1982, 401
JACS 1987, 1746

Noyori:

JACS 1987, 1596
JACS 1995, 1017
JACS 1995, 2675
JACS 2001, 7473
JACS 1995, 7562
JACS 1997, 8338
ACIE 2001, 2818
JOC 2003, 1998
JACS 2013, 2604

Asymmetric and Catalytic Conjugate Addition Reactions #chempaperaday 134-143

JACS 1979, 4236
ACIE 1998, 2099
Tetrahedron 1989, 349
JACS 2000, 1826
Chem.Rev. 2012, 2339
Chem.Soc.Rev. 2009, 1039
JACS 2005, 6877
JACS 2008, 446
JACS 2010, 14315
ACS Catalysis 2012, 95