Artificial polymerases

The development of synthetic catalysts that has parallel enzymatic efficiency in terms of rate and turnover is still a challenge in chemistry. The de novo design of a biochemical system in a molecular matrix is fascinating and challenging for future synthetic catalysis. We recently used a non-covalent interaction approach to create nano-sized artificial enzymes for the size, shape, stereo, and enantio-selective synthesis of small molecules and polymers.

 

These biomimetic systems not only provide fresh insight into elucidating the catalytic mechanism of natural enzymes but also demonstrate the underlying principles in structure-based catalysis. The newly discovered chiral catalytic host can move along polymer chains in a single direction like natural enzymes, polymerases, and ribosomes. Such synthetic catalytic machines could be used for the synthesis of sequence-controlled polymers as well as for data storage.

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.

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.

Useful chemicals and fuel from carbon dioxide

Carbon dioxide is an abundant, non-toxic, inexpensive, and renewable source of carbon. This makes CO2 the most coveted compound by Green Chemistry enthusiasts. Industries are always on the lookout for ways to enable the effective use of to act as synthetic building blocks for producing fuels like Methane, Di-methyl-ether, and Methanol fine-chemicals. Furthermore, CO2 conversion could also help reduce atmospheric CO2 levels, popularly known as “Green House Gas”, and thus, protect the climate.

Nature has been highly successful in using CO2 as synthetic building blocks in photosynthesis. For decades, scientists have been trying to understand this phenomenon at a molecular level. Such studies have proved useful in developing biomimetic catalysts for CO2 conversion. Chlorophyll (Porphyrin molecules) in green plants convert incident sunlight and atmospheric CO2 into sugars (energy). So, this makes them a promising target for testing activation catalysts for CO2 adsorption. Effective CO2 adsorption using man-made catalysts is indeed our end-goal. Much research is being conducted in this area to further the economic viability of the processes that utilize CO2. Several companies are pursuing the idea/concept of thermochemical and electrochemical conversion of CO2 into chemical feedstock or polymers. Research and development are currently focused on increasing the catalyst life and bringing down the temperature of conversion.

Future research must emphasize the rational design of highly active catalysts to satisfy the economic development of CO2 conversion. However, the development of such efficient catalysts requires a complete understanding of CO2 and CO2-catalyst interactions.

In order to develop such a catalyst, the following points should be considered,

1. CO2 has a strong affinity towards nucleophiles and electron-donating reagents due to its carbonyl-carbon's electron deficiency; if the designed catalysts has nitrogen or base-functionality (basic), it will have an increased affinity towards CO2 (e.g., Porphyrin, Grignard reagents).
2. With low-valent metals and alkene, CO2 undergoes “oxidative cycloaddition.”
3. New CO2 soluble catalysts may increase efficiency.
4. Homogeneous catalysis in compressed CO2 may increase selectivity.
5. The catalyst in supercritical CO2 may also increase stability. It is essential to use CO2, based on the unique physical properties as that of the supercritical fluid, either as a solvent, or as an anti-solvent, or reactant, or a combination of all.
6. Photoelectrochemistry, the study of using solar energy to split CO2, is an emerging method for clean production of chemicals. It is also essential to develop catalysts (Semiconducting materials) for the electrochemical conversion of CO2.
7. The use of high-energy starting materials may ease the catalyst role.
8. The catalyst will be more efficient if it has both CO2 adsorption and activation functionality. E.g., designer MOF that contains Lewis-base sitewill donate electron to CO2, in contrast to the Lewis-acids sites in traditional MOFs for adsorbing CO2.
9. A computational tool such as Density Function Theory (DFT) may help improve the catalytic activity or find a new catalyst.
10. Chemical reactions can also benefit from using CO2 as a mild oxidant or as a selective source of O2 atoms because dissociation of CO2 on a catalyst-surface could produce active O2 species.

The trend towards converting CO2 to valuable chemicals and fuels will probably intensify in the near future. This could, in turn, lead to effective management to tackle climate change and the energy crisis.

As Whitesides emphasizes, managing CO2 and conversion into valuable chemicals and energy will be the reinvention of chemistry, and it is also a chemistry/ molecular solution to the critical problem facing society. He says

 “Some of the most interesting problems in science, and many of the most important facing society, need chemistry for their solution. Examples include: understanding life as a network of chemical reactions; interpreting the molecular basis of disease; global stewardship; the production, storage, and conservation of energy and water; and the management of carbon dioxide."

Issues pertaining to CO2 are truly global and a major opportunity to develop sustainable energy options and environmental preservation. So, the use of CO2 to synthesize useful chemicals & fuels will mark a new field in chemistry. It is important to establish university-industry-collaboration to search for new-reactions & new-catalysts in this field.

Artificial Photosynthesis using graphite Carbon Nitride

Fine chemicals and hydrogen production from water, carbon dioxide, and solar energy are ideal future chemical and energy sources independent of fossil reserves. The development of new functional molecular materials (catalyst) for the application in fine chemical and clean energy production using water and solar energy is fascinating and quite challenging because the catalyst must be sufficiently efficient, stable, inexpensive, and capable of harvesting light. 

Polymeric graphite carbon nitride (C₃N₄) materials are commonly available simple semiconductor photocatalysts. It is being non-volatile up to 600⁰C even in the air with no detectable solubility or reactivity in conventional solvents, including water, alcohols, DMF, THF, diethyl ether, and toluene. Carbon nitride is considered to be extremely stable and basic in nature. It can be used as the multifunctional heterogeneous catalyst for fine chemical and pharmaceutical synthesis as well as a good organic semiconductor due to its right bandgap (2.7 eV corresponding to an optical wavelength of 460 nm). 

Prof. Markus Antonietti and his team at Max Planck Institute of Colloids and Interfaces in Germany, have successfully split CO2 or photochemically turn water into hydrogen and oxygen using graphite carbon nitride. However, only four micromoles of hydrogen per hour were produced out of the researcher's reaction vessel (quantum efficiency of the Pt modified CN is approximately 0.1% with irradiation of 420-460 nm). This opens the door to artificial photosynthesis and produces chemicals and energy from greenhouse gas /solar energy. It will contribute to the prevention of global climate change. 

Nano reactions

Recently, nanoporous materials have emerged as important and efficient heterogeneous catalysts for organic transformations due to their excellent textural characteristics, including high surface area, large pore volume, uniform pore size distribution, and simplicity in workup recyclability. The pore diameters are chosen to control the access of molecules to the catalytic reaction sites located inside the porous cavities. Only the molecules of specific sizes and chemical properties are selected and guided to the reaction centers, where they are efficiently transformed to the desired products.

Cyanation of aryl halides

There are several methods available for the cyanation of aryl halides. However, a common problem with many of the more traditional methods is that they are very toxic# One method to full fill these criteria has been around for a while (Weissman S A et al., J. Org. Chem.2005, 70, 1508-1510.)

  Figure: Ligand-free, palladium-catalyzed cyanation of aryl halides. 

Potassium hexacyanoferrate(II) has been used as a cyanide source. This result increases the list of metal-catalyzed reactions that can be performed without ligand.

This method's advantage is obvious; in contrast to other cyanating agents, potassium hexacyanoferrate(II) is less poisonous# and can be handle without special precaution due to the slow release of cyanide ions. Additionally, it significantly improved catalytic productivity compared to know procedures achieved previously.

#( KCN is extremely toxic (LDL0(oral, human) =2.86mg Kg-1 and develop HCN on contract with acidic water. K4[Fe(CN)6]­ is non-toxic and used in the food industry for metal precipitation in wine. Also, it has been used as an anti-agglutinating auxiliary for NaCl (table salt). It is soluble in water without decomposition. Schareina T et al, Chem Commun., 2004, 1388-1389.)

Reduction of amino acids

There are many ways to reduce amino acids to amino alcohols; using sodium borohydride and iodine in THF is an excellent process. This methodology is not only nonexpensive and safety perspective, but the workup is much easier (compared to LiAlH4).

Iodine oxidizes the hydride giving a mole of H2 and generating BH3 in situ. All that borane actually the stuff that reduces the acid to alcohol.