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