Sunday, December 7, 2014

Nobel Prize 2014 : Chemistry Front Runners & Winners



Dear Readers 

December is upon us and there is a sense of excitement, a sensation of general electricity in the air and about each and every one of us. Perhaps it’s the rush of serotonin from the expectation of the upcoming Christmas celebrations or better yet the utter thrill of participating in the Feast of Winter Veil. Aahhh the memories, it truly is a time for remembrance, reminiscing and rejoice. 

But apart from the solstice festivities I am reminded of yet another event that is a combination of December, serotonin and remembrance. Yes! The 2014 Nobel Prize ceremonies are just around the corner and I am left with the recapitulation of the Chemistry awards to complete the holy trinity of Nobel prizes, for 2014.

And before you say it I am fully aware that I left out the other two awards , but the sole purpose of this omission is due the fact that I wanted to create some controversy before I started the article, and I daresay …….……………people have better things to worry about.

CHEMISTRY












 Ching W. Tang and Steven Van Slyke: Organic Light emitting 
diode 

 It was truly a “Kodak moment” (a reference I’m sure will be missed by the younger generation) when Ching W. Tang and Steven Van Slyke, whilst working at Eastman Kodak Research laboratories, published a paper unveiling  their experiments using electricity to  activate organic chemicals  so that they  generate light ,in a process that was quite energy efficient.


Praise and citations (over 9000!!!!!!! for their papers released in 1980s) followed suit this revolutionary technology which changed the very landscape of electroluminescence. 

A template of the diode would consist of two layers of different semi conductor organic materials squashed in between two electrodes which emitted light when a small charge was passed through the system. This needed far less power (10V) than previous versions of electroluminescent diodes (100V).

As illustrated in the diagram the first layer would be the cathode, magnesium/silver alloy was originally used by the duo. Next came the luminescent or emissive layer of tris (8-hydroxyquinolato) aluminum (Alq3) which was followed by a conductive layer of a diamine. The Anode layer of indium tin oxide would be last. All the layers are deposited, in very thin films, on a substrate usually glass or plastic. 

The reaction when a current is passed through the diode, instigating freed delocalized electrons of the Alq3 to come into contact with the holes of the diamine layer, is the sole cause of its incandescence. Ching and Steven’s rudimentary version, which had a luminous intensity peak of 550nm, visibly representing green, was improved upon by the use of better organic polymer layers and improved electrodes to host the full scope of the color spectrum. 

The appliance of OLEDs can be seen the world over, from your TV screen, to your mobile display, to your camera and even to your hand held game consoles. The innumerable applications of their invention earn the duo a well deserved nomination as they kick start our list.

Steven Van Slyke (right) and Ching W.Tang (left)
 


Charles T. Kresge, Ryong Ryoo, Galen D. Stucky: Modeling Mesoporous Materials 

There are three types of nanoporous mediums, macro (pore size: 50–1000 nm), meso (pore size: 2–50 nm) and micro (pore size: 0.2–2 nm).  Mesoporous materials are considered bulk materials with large internal surface areas of up to 1000 m2/g. Compounds of silica and alumina are the more common mesoporous materials. Their applications range from catalysis, sorption, ion exchanges, optics, photovoltaics, for use in bio-sensors and as molecular sieves.

Charles Kreger
It was Charles Kreger who first demonstrated that such materials could be fabricated and customized in a laboratory, receiving more than 11,500 citations for his paper in Nature publications. The key to his innovative creation process was the use of surfactants, a compound that reduces surface tension of liquids. It was surrounding the resultant micelle; formed from the inclusion of surfactants in its synthesis, that the aluminum silicates grow. The size of the pores depended upon the molecular structure of the surfactant used. 

Ryong Ryoo
Using this process Kreger synthesized several types of mesoporous materials (MCM-36, MCM-56, MCM-67, MCM-68) the most famous of which is MCM -41(Mobil composition of matter No. 41). 

MCM 41’s most notable predicted application is as a drug delivery system for a cytotoxin to attack cancer cells. 

Enter Ryoo, not the Hadouken hurling Japanese street fighter but rather the award winning Korean chemistry professor. His research at KAIST University focused on mesoporous carbon, specifically on a hard templating synthesis strategy where mesoporous silica were used as scaffolding around which were built carbon based structures. The silica template was later removed leaving a framework of 3nm carbon mesotubes or mesopores (which was later found out to be tunable to twice that size). 
Galen D Stucky

Mesoporous carbon has several applications especially in the area of fuel cell engineering serving as a catalyst support for platinum nanoparticles, used to enhance the rate of half reactions in a fuel cell. 

Additionally the fabrication process itself offers a smart new synthesis strategy applicable to other nanoporous materials. 

Dr. Galen D. Stucky of the infamous Stucky group demonstrated how hexagonal mesostructures with 7nm -30nm pores could be fabricated. Thus was born the Santa Barbara Amophorous No.15 named after the University of California. SBA 15 is used as a drug delivery system especially for poorly water soluble drugs and it is also used as a biosensor.

 For their contributions to the fabrication, customization and improving of the functionality of mesoporous materials, not to mention their future implications and applications, these gentlemen are more than worthy of the illustrious Nobel.

 
Graeme Moad,Ezio Rizzardo and San H. Thang: RAFT Polymerization


From paints to plastics to plates to cups to carbon fiber to rubber to adhesives, Polymers are core components of most of the current technology we see around us.  As such their synthesis, known as polymerization, has become a vital part of modern industry.   Polymer use and synthesis date back to over 70 years; however in the 1990s three chemists working at the Commonwealth Scientific and Industrial Research Organization (CSIRO) centre in Clayton, Melbourne in the land down under, blew previous polymerization techniques asunder. 

Their work particularly revolved around solving the controllability issue of the radical polymerization process which was used to produce polymers such as polyacrylate, polyacrylonitrile, polystyrene, and polyvinyl acetate. This was one of the more direct techniques and involved using a free radical molecule to initiate a repetitive chain reaction between monomers so that they bind together to form a polymer. Alas this repetitive chain reaction’s termination was unpredictable and the entire polymerization process, if not monitored, was found to be extremely hazardous. 

After much research Graeme, Ezio (not from Assassin’s creed) and San discovered that they could control the radical polymerization by introducing a transfer agent in the form of a thiocarbonylthio compound that offered versatility to the process. This transfer agent allowed the control and manipulation of the generated molecular weight and the dispersity of the polymer. It also enabled reversibility. This is due to the fragmentation reaction that occurs resulting in either the starting polymeric species or a radical and a polymeric transfer agent from which the radical or the polymer species can be removed to essentially reverse the process.  Hence the trio named the process “Reversible Addition-Fragmentation chain Transfer” or RAFT. 

San H Thang (left), Ezzio Rizzardo (middle) and Graeme Moad (right)
RAFT polymerization made way for the synthesis of a variety of polymer types with complex architectures, controlled molecular weight and low dispersity. The flexibility it offers allowed the meshing of a wide blend of monomers to make co-polymers and also enabled the process to be conducted in a range of solvents without any temperature restrictions. 

For their development upon the radical polymerization process by introducing, to the world, the RAFT synthesis system these gentlemen earn a laudable nomination to join the ranks of the Nobel laureates. 

Kenichi Honda and Akira Fujishima: Water photolysis

Photolysis refers to the breaking down of a compound with the use of photons; this is most commonly seen in photosynthesis as water is oxygenated to form two hydrogen atoms and a diatomic oxygen molecule which is released into the air. Plants, thylakoids of cyanobacteria and the chloroplasts of green algae naturally use photolysis in the process of creating chemical energy. 

However the recreation of the water photolysis process proved to be difficult as just shining a light did nothing to water. 

It was in 1972 that Akira Fujishima and his mentor, the late, Kenichi Honda devised a simple method to artificially reconstruct this process. They would spilt H2O by incorporating Titanium dioxide as a catalyst and subjecting it to UV light. This process is known as Photocatalysis.

The discovery of the photocatalysis of water has several implications and quite a few applications.
The most obvious and central use is that the hydrogen gas that is formulated offers a clean, renewable and inexpensive source of energy and therefore research is being carried out ,feverishly, to develop practical photochemical hydrogen fuel cells for mass consumption and commercialization. 

Akira Fujishima
Catalysts other than titanium dioxide are being tested to find an effective and efficient way of yielding hydrogen gas however due to the fact that an inordinate supply of input energy is required for the process the main source of hydrogen remains to be natural gas. 

Kenichi Hond
Photocatalysis is also used to disinfect water in a process called Solar water disinfection. Although water disinfection can be done without using a catalyst, recent studies have shown that using such an agent like titanium dioxide augmented the effects of solar irradiation. Even though the process isn’t quite efficient photocatalysis disinfection requires no energy input and the materials involved are quite stable thus maintaining its appeal as a viable process, applicable especially in remote areas. 


Akira and Kenichi’s contribution made way for avenues of research in both the invention of a much needed energy source for the future and the equally needed purification of polluted and infected water. Thus it is only just that they receive their rightful acclamation for the Nobel Prize. 

 
Jacqueline K Barton: DNA ET, Metallo DNA Binding probes, DNA electrochemistry 

To Jacqueline Barton the body was a complex machine with DNA representing its molecular wires. This unorthodox outlook stemmed from being an inorganic chemist and it is this perspective that led her to experiment and examine the interactions between metal complexes and DNA. 

Jacqueline pioneered the application of these organo-metal complexes to probe the “pie” stacked double helix structure of DNA. She synthesized two classes of probes, each designed to interact with DNA in a specific manner. Rhodium complexes would photocleave the sugar phosphate backbone of the DNA near its binding site and Ruthenium complexes would illuminate after binding. Unlike Organic complexes they can be manipulated into different modules integrated with recognition elements. These complexes once intercalated allow for DNA sequence recognition. 

Whilst tuning metal complexes for DNA sequence recognition Barton and her team stumbled upon the capability of certain complexes to recognize single base mismatch pairs. Thus was born a third class of organo-metal complexes, christened metalloinsertors. Using Crystallography and Nuclear magnetic resonance spectroscopy (NMR) they were able to examine the binding process of metalloinsertors. The sterically expansive ligand of the metalloinsertor would be inserted into the DNA’s minor groove to eject the mismatched pair into the major groove to allow for access. This would be the first ever observation of a small molecule insertion of DNA.  

The applications of the DNA binding probes range from the early detection of cancer and contribution to chemotherapeutics to hampering the proliferation of mismatch repair deficient cells to drug delivery systems.
However this was but only one of her contributions. The next would be aided by the prior discussed research. 

Jacqueline K Barton along with Bernd Giese and Gary B.Schuster conducted the first research to demonstrate that aside from carrying our valuable genetic information DNA is also responsible for the transfer of electrons, for which they earned a Nobel nomination in 2009. 

Electron transfer (ET), as it was acceptably theorized by Nobel winner R.A Marcus and improved upon by N.S. Hush, referred to the quantum mechanics of the redox process wherein electrons are gained by an acceptor molecule (reduction) and lost by a donor molecule (oxidization).There are three main ways in which the transfer can occur. The electron can travel along an established ligand bridge or transition through temporary bridges or circumvent this process and hop straight to its destination. 

 Numerous biological processes, like photosynthesis, were also found to have ET chains and it was experimentally observed that DNA was quite an exceptional medium for the transfer and transportation of electrons. 

Jacqueline likened the double helix π stacked structure of DNA to a wire, used for long range signaling between proteins in a cell. However DNA frequently gets damaged by the metabolic activity in our bodies and environmental factors such as radiation. In such a scenario signaling will be impaired. These DNA lesions, if you will, are constantly repaired by special proteins synthesized by our cells. Like the late Jedi council the fixer proteins constantly keep in touch through the force (DNA) and actively seek out disturbances (damages) in it. However when repair proteins get corrupted by power and they turn to the dark side entire cells are defiled becoming cancerous. 

Star wars analogy aside this discovery would be a crucial stepping stone to the development of DNA based electrochemistry. 

It was evident that the use of ET as a reporting and signaling system to locate DNA damage and lesions was vital for the operation of DNA repair; however its function is assumed to extend beyond that of the DNA repair process. Transcription factors such as SoxR oxidative stress regulator and p53 related to tumor regulator cells are also believed to use the ET system. 

The Barton Group residing in Caltech are using DNA’s ET system to develop a highly sensitive mode of detecting DNA binding proteins and mRNAs. 

An electrochemical approach they are focusing on is depositing a self assembled monolayer of Thiol modified DNA, inserted with a redox- activate probe, onto a gold surface. The reduction of the redox probe within the DNA enables the analyzing of the DNA’s structure in the section between the gold surface and the probe, to uncover DNA lesions, mismatches and even protein based interactions like DNA base flipping. 

Research is being conducted into incorporating new redox probes and surface passivation strategies to make this a feasible analytic procedure for the detection of protein and mRNA. The development of a gold multiplex chip to conduct several DNA analysis simultaneously with the least amount of sample preparation holds great promise in the field of pathology detection, especially for exposing cancer transcription factors. 

Jacqueline K Barton


For her continous efforts and contributions, which are products of her daring outlook and ideals on DNA, Prof.Jacqueline Barton deserves approbation and acclamation and a nomination for the Nobel Prize. 


The winners of 2014 Nobel Prize in Chemistry 

Eric Betzig, Stefan W. Hell and William E. Moerner: super-resolved fluorescence microscopy

“For a long time optical microscopy was held back by a presumed limitation: that it would never obtain a better resolution than half the wavelength of light. Helped by fluorescent molecules the Nobel Laureates in Chemistry 2014 ingeniously circumvented this limitation. Their ground-breaking work has brought optical microscopy into the nanodimension” ~NobelPrize.org

This beyond revolutionary advancement ushered in the age of observable, optical nanoscopy sending shockwaves throughout the fields of biology.  

The journey began with Prof.Stefan Hell who upon the finishing his Ph D embarked on a quest to prove the infamous Abbe wrong. No, it wasn’t the 16th president of the United States that he wanted to challenge but Professor Ernst Abbe, who in 1973, set in stone, the law of limited resolution. It stated that the observation of objects smaller than 0.2 micrometers (half the wave length of light) was pure ludicrous. However after watching the Ten commandments we all know what happens to laws written in stone. 


Stefan Hell
But as all rebels do, he was met with harsh admonishment, cold discouragement and many an obstacle, which made him finally decide to leave Germany. So it was that the ambitious young Stefan Hell found himself in Turku where he was taken in by a scientist, working on fluorescence microscopy, and asked to join his research team. Whilst laboring in the library of the University of Turku, he stumbled upon a tome titled “Quantum Optics” and in it he would find his first guiding muse “stimulated emission”

Fluorescence microscopy involved using fluorescent molecules (e.g. antibodies) to join with cellular components (DNA) for imaging purposes. This enables scientists to see where the component is located however its resolution, or lack thereof, prevented clear observation of small molecules.

After reading about stimulated emission he noted that in a state of population inversion, it could optically amplify the incoming light due to its ability to reduce the energy of excited molecules thus creating photons with the same phase, frequency, polarization, and direction of travel as its source incident wave.

It dawned on Stefan Hell that incorporating stimulated emission into fluorescence microscopy would essentially provide the answer he sought.

One light to fluoresese them all
Another to quench them
Two lights to find them all
and in the darkness clarify them

In 1994 he published a paper proposing a method where two light pulses were to be used, one to excite all molecules and then the second to extinguish fluorescence in all molecules but the ones left in a nanometer sized gap in the middle which would be imaged. By carefully scanning the sample, nanometer by nanometer, a detailed image can be modeled. Its significance was that the resolution depended on the amount of fluorescence registered at a given point thus rendering resolution essentially limitless.   

He dubbed his method Stimulated Emission Depletion (STED) and in the wake of Y2K managed to successfully image an E.Coli Bacterium with resolution unattainable by a regular microscope.  However, unbeknownst to Stefan Hell, other forces were at work trying to achieve the same goal; although in a quite a different manner. 

The year was 1989; In an IBM research center in San Jose California, W.E Moerner became the first scientist to measure the light absorption of a single molecule. All chemical experiments were to that point conducted by observing a collection of molecules from which a mean was derived to represent a standard molecule. Moerner’s breakthrough meant that chemists could now use techniques to assess single molecules thus improving our understanding of molecular chemistry. 

As fate would have it Professor Moerner moved to San Diego, in 1997, to join the University of California, right about the time when upcoming Nobel Laureate Roger Tsien was meddling about with his discovery, the Green Fluorescent Protein (GFP) that he extracted from a jellyfish. He was trying to make the protein fluoresce with colours other than green. What was fascinating about GFP was that, when bound to other proteins in a cell, it would make them visible, acting as a marker system with which the location of a bound protein could be observed. 

Moerner was intrigued by this and experimented with GFP. He found a variant of it which could essentially be switched on and off by subjecting it to a specific light wave length. After initial excitation, at 488nm wavelength, it would eventually fade away, but would only be reactivated at the wavelength of 405nm.
In an experiment he scattered these proteins in a gel, at intervals larger than Abbe’s diffraction limit and found that it was indeed possible to observe single molecules that fluoresce through an optical microscope. Moerner likened them to optically controllable little lamps and published his findings in Nature publications, 1997, which landed in the hands of Eric Betzig. 

Eric Betzig had managed to already surpass Abbe’s law by the start of the 1990s. He used a thin tip placed only a few nanometers away from the specimen surface to emit light in a method called near field microscopy.

However near field microscopy could not visualize anything below the sample surface and it was soon evident that it could not be improved further. Depressed he quit his research career at Bell labs, yet Abbe’s diffraction law still haunted his mind.

Perhaps it was the chill of that winter’s day but something sparked a thought in his mind. Whilst working on his near field microscopy, the exploits of other scientists particularly one W.E Moerner had compelled him to observe a fluorescent molecule using his special microscope. A query formed in his mind whether the use of fluorescent molecules of different colors could possibly enable him to circumvent the diffraction law using a regular microscope. 

He formulated an answer by suggesting that fluorescent molecules of different colours, possibly red, green and yellow, be spread out in intervals of distances greater than Abbe’s 0.2 micrometers limit. A microscope would be set to register one image per colour and all images when superimposed would give a high resolution image where single molecules, due to their distance apart and different colours, could be observed. He published his theory in the journal of Optics Letters, but still wasn’t ready to return to the world of research and academia.  

It was during this time that he came across literature about the GFP. It renewed his passion for research since now; the possibility of implementing his theory was within his grasp. However it was in 2005 that the fruition of its implementation grew ever closer, with Betzig’s discovery of a protein,similar to the one Moerner found, that could be optically controlled. This led to the revamping of his hypothesis as it wasn’t necessary for the fluorescent molecules to possess different colours anymore; they just had to fluoresce at different times. 

His 11 year long wait was rewarded in 2006 as he, along with other scientists working with fluorescent proteins, demonstrated the applicability of his theory. They used a weak light pulse to temporarily excite small groups of fluorescent proteins (which were spaced at distances greater than 0.2micrometers) at a time, per image. The superimposition of these images gave them a detailed comprehensive and high resolution image which shattered Abe’s law of diffraction. His victory was final once he published his work in Science publications. 


Our epic trio still continues to tirelessly strive for progress, as they spearhead research in the field of 
nanoscopy. Their contributions resulted in the techniques of nanoscopy used around the globe. Stefan hell himself has seen the inside of a living nerve cell and looked upon brain synapses. W.E. Moerner has examined proteins related to Huntington’s disease. Eric Betzig has witnessed the wonders of cell division inside embryos. This tool they have forged has enabled us to visually observe the most minuscule elements that make up life so that we may better understand it.

Make sure you tune in on the 10th to witness the celebrations as the winners of this year’s prizes officially join the ranks of the Nobel laureates. 

I hope you have a wonderful winter or, if you are in the southern hemisphere, a smashing summer ahead of you 

Cheers.

                                                                             

 



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