Old wisdom new tools

Some of the shapes depicted in ancient artifacts that were invisible to the human eye came into view with the advent of 20th-century tools. Some being nano and microstructures. These tools also help chemists to see the formation of chemical bonds in real-time. 

The rapid development of modern nano-technological tools such as the Atomic Force Microscope (AFM), Scanning Tunnelling Microscope (STM), and Laser Scanning Confocal Microscope (LSCM) allow scientists to invent, explore and validate old scientific discoveries. From the perspective of scientists involved with chemistry, it helps to manipulate atoms and molecules precisely for the fabrication of macroscale products as well as to look at the real-time covalent bond formation in a single molecule. Observing chemical reactions by force microscopy at sub-molecular resolution has been reported by de Oteyza et al. They reported the atomically resolved imaging of a complex molecule as it undergoes a chemical reaction on a metal surface.

In addition to the normal covalent bond formation, very recently Wilson Ho et.al., revealed the image of hydrogen bonding in porphyrin molecules using chemically modified STM tip, enlightening us with the rapid advance in this field. These developments will have a huge impact in nanoscience especially in the field of single molecular electronics and bottom-up fabrications. This new evolution of molecular nanotechnology will bring chemists, physicists, engineers, and biologists together.

How practical is it to prove old theories with modern, technologically advanced tools? Is it really possible? However, if it is indeed possible, would it be a landmark achievement that would push chemistry into a new era, in the coming years? Let me exemplify. Mayan blue is a bright blue pigment that had been used by Mayans about 2000 years ago to paint murals. The distinct feature about these murals is that the Mayan-blue has withstood the wrath of weather over centuries, and refuse to fade even to this day. on the On the other hand, even the most advanced of paints of today, tend to wear off after a couple of years of harsh weather and negligent maintenance. This is a phenomenon that has baffled scientists for several years. They were able to gain some insight into this in the recent past with the help of modern nanotechnological tools. The Mayan dye is based on Indigo dye, which is trapped in a porous fame work of clay called palygorskite. The silicate hull forms a protective layer around the dye molecules. This prevents the dye pigments from directly interacting with the forces of nature and other interferences such as organic solvents, acid, and alkali treatment, etc.

It is the Mayan's ingenuity at developing the pigments for Mayan blue that has set them eons beyond outreach. Reverse engineering could help us understand its structure and shed some light into the properties of advanced hybrid materials. Maybe, the day is not far off when we are able to decode this chemical phenomenon and come up with commercial paints that will last forever.

Cooperative Catalysis

Cooperative catalysis occurs when the synergic catalytic effect of at least two different entities acts together, increasing the rate of a chemical reaction beyond what is possible when either of the two entities is used independently. The idea of “Cooperative Catalysis” has inspired synthetic chemists to create artificial dual activation catalysts. Such a Cooperative Catalytic pathway is often used in enzymatic catalysis. Enzymes are continue to be a source of inspiration for (designing and) developing new catalytic reactions that are high in efficiency & selectivity and minimal waste.

Urease is a dinuclear metalloenzyme which catalyzes the hydrolysis of urea into carbon-di-oxide and ammonia. The dimeric nickel center of this enzyme is (the active site) responsible for cooperative catalysis. Urea co-ordinates with one Ni-center, thus activate the electrophile (act as Lewis Acid), whereas water coordinates with the second Ni. It is thus acidified and can be deprotonated by histidine to generate hydroxide as a nucleophile (generate nucleophile), which is, now in close to the electrophile, and, can attack in an intramolecular fashion.

A similar cooperative catalytic activity with Bronsted and Lewis acidities can be generated by simultaneous incorporation of multiple elements in the silica framework is quite interesting and holds promises of unprecedented catalytic performances.

We recently prepared a similar natural mimic, a bimetallic nano-porous catalytic system, which would be able to perform cooperative catalysis for the selective synthesis of ortho-prenylated phenols and 2,2-dimethyl chroman, starting from phenol and allylic alcohol. Prenylated phenols are widely distributed in nature and are known to be an important structural unit of pharmaceutical compounds. Similarly, 2,2-dimethylchroman derivatives also exhibit broad range of interesting physiological properties, we are able to synthesis the important structural motif by using the new cooperative catalytic systems.

The amount of aluminum present in the framework dictates the acidity of the catalyst, and by fine-tuning the aluminum content, we can develop the catalyst with the desired catalytic property. Catalyst developed in such a manner was found to be highly active and selective. The products obtained were good and satisfactory. Additionally, the synergistic effect of the bimetals (Cu and Al) in the nanoporous catalysts controls the selectivity of the final products.

Nobel Advice

Are you a Nobel aspirant, young researcher, or want to be part of good science? Here is an advice from Prof. Avram Hershko ( Winner of 2004 Nobel Prize -for the discovery of ubiquitin-mediated protein degradation)

Here is a lesson from his life in science that he presented at the Lindau Nobel Meeting 2013."

• It is very important to have good mentors- you cant learn how to do good science just from reading the literature.
• Find an important subject that is not yet interesting to others the big guys will get there before you! Do not go with the mainstream. 
• Accidental observations may be the most important ones. Grab your Luck. 
• Use whatever experimental approach is needed for your objective. It may not necessarily be the most fashionable (“state-of-the-art”) technology. Of course, biochemistry will always be needed. 
• Science should be a curious driven adventure. You should have a lot of excitement and fun. 
• Never leave bench work, and shall continue to get a lot of excitement and fun.

Inspired by Nobel

It is a great honor, not to mention my good fortune as well, to be nominated and sponsored by Department of Science and Technology, India, as one of the 23 young researchers who will be attending the 63rd Lindau Nobel Laureate Meeting as part of the Indian delegation.

With much anticipation, I await to listen to the eminent speakers at the Lindau stellar, who need no elaborate introduction. The work of most of the scholars have formed a basis for my own work as well as for thousands of other scientists and students around the world. We ceaselessly draw inspiration from their work. I have long admired these scholars, but to listen to them in person would be an awe-inspiring experience, which I am sure would vouch for it.

“It is the quest for knowledge that drives the scientific community.” Armed with this belief, I look forward to meet and interact with personalities of scientific excellence at close quarters. The informal setting at the Lindau Meeting, I hope, will allow us to discuss our work in a relaxed manner. I believe this meeting will be a great platform to learn directly from the masters and to meet peers from across the globe.

Read More at the Lindau blogs website

Click Chemistry for Pyrrole Synthesis

The Pyrrole heterocycle is an important chemical motif, found widely in pharmaceuticals, natural products, agrochemicals, and advanced materials. The introduction of new methods or further the work on technical improvements in order to overcome the limitations (such as low efficiency and selectivity) found in pyrrole synthesis is still a pressing experimental challenge. 

The concept of “Click Chemistry” is gaining rapidly due to its high efficiency, selectivity, and yield under mild reaction conditions with a wide variety of readily available starting materials. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) has emerged as the premier example of click chemistry and plays a significant role in organic synthesis. 

Prof. Aiwen Lei and coworkers, Wuhan University, Hubei, have developed a silver catalyst “click reaction” for the synthesis of pyrrole, by cycloaddition. This system benefits from readily-available starting materials, low catalyst loading (0.1 eq), short reaction times (2 h), and excellent chemo-selectivity. Moreover it works for both internal and alkyl-substituted terminal alkynes in the presence of many functional groups. The extremely mild conditions used make this reaction synthetically attractive. 

This mechanism involves the formation of silver–acetylide complex and silver–isocyanide complex. Subsequently, the cyclo-addition between complexes would afford the key intermediate complex to be followed by protonation and tautomerization of the intermediate complex to form the desired product. 

The catalytic synthesis protocol tolerates many functional groups, including methylthio, methylsulfonyl, and ethynyl groups. Moreover, alkyl-substituted terminal alkynes were also found to be suitable reaction partners. Interestingly, both Cu(II) and Cu(I) turned out to be ineffective.