Advancement in Modern experimental Chemistry.pptx

This presentation discusses advancement in modern experimental chemistry.

1. Excitements of Modern Chemistry Kamaljit Singh Professor of Organic Chemistry Department of Chemistry, Guru Nanak Dev University, Amritsar Scientific Social Responsibility , SERB, DST, Govt. of India

2. Organic Chemistry: A Science of Art, Imagination, Creativity and Human Behavior

3. Importance of Organic Synthesis The organic chemist is more than a logician and strategist, he is an explorer strongly influenced to speculate, to imagine, and even to create. These added elements provide the touch of artistry which can be included in a cataloging of the basic principles of synthesis but they are very real and extremely important. E. J. Corey, 1967 There is excitement, adventure and challenge and there can be great art in organic synthesis R. B. Woodward, 1956

4. Interesting Elements of Organic Synthesis Great Complexity and variety Challenge verging on impossibility Demand for both mental and manipulative rigor Dedication, persistence and hard work Never-ending advances in sophistication Unlimited opportunities for intellectual excitement and satisfaction Strong coupling with all areas of chemistry and also biology and medicine Relevance, at very fundamental level to human well-being, health, and education

5. ORGANIC SYNTHESIS Target Oriented (Total Synthesis) Methods Oriented Natural Products Designed Molecules Reagents Catalysts Synthetic Strategies Synthetic Tactics Materials Science Interesting Molecules Biologically Interesting Molecules Theoretically Interesting Molecules Medically Interesting Molecules

6. Target Molecule Synthesis There is no denying (nor should there be any need to deny!) that the sheer sense of challenge posed by a complex molecular target serves to stimulate the creative impulses of the synthetic chemist. S. J. Danishefsky, Aldrichimica Acta, 1986 The synthesis of substances occurring in Nature, perhaps in greater measure than activities in any other areas of organic chemistry, provided a measure of the condition and power of Science. R. B. Woodward, 1956

7. Synthetic Chemistry and Total Synthesis Synthesis = The process of putting together In defining strategies and reactions to construct complex molecules, we require synthetic methods that can perform a wanted structural change and none other (i.e. chemoselective ) orient the reacting partners in a correct fashion (be regioselective ) create the correct orientations of the various parts of the molecules with respect to each other (be diastereoselective ) enable the formation of a molecule of one handedness or a mirror image isomer (be enantioselective ). Such extraordinary demands are exciting challenges. B. M. Trost, Science 1985, 227, 908

8. Vitamin B 12 (1973) R. B. Woodward and A. Eischenmoser Pure and Applied Chem. 1973, 33, 145

9. Palytoxin (1994) 64 stereogenic centers, from which over 10 19 different stereoisomers could exist Kishi, Y. J. Am. Chem. Soc. 1994, 116,11205

10. Brevetoxin B (1995): marine neurotoxin K. C. Nicolaou, J. Am. Chem. Soc. 1995, 117 , 1171 and 1173

11. Ciguatoxin : Neurotoxins present in sea-fishes. LD 50 = 0.25-4 mg/kg M. Hirama, Science , 2001, 294 , 1904

12. Calcheamicin g I 1 (1992): High potency against tumor cells K. C. Nicolaou, J. Am. Chem. Soc. 1990, 112, 8193

13. Taxol (1994): Anticancer compound K. C. Nicolaou , Nature 1994, 367,630

14. Ladderane Dodecahedrane Paquette, Chem. Rev. 1989, 89, 1051 G. Mehta, Angew chem. Int. Ed. 1992,31, 1488 Aesthetically Designed Molecules

15. Dendrimer moleclule: 125A o in diameter Xu, Z; Moore, J. S. Angew Chem. Int. Ed. Engl. 1993, 32 , 1354

16. Light Harvesting Arrays J. Am. Chem. Soc. 1994, 116 , 10578

17. Philosophical Aspects of Synthesis Chemical synthesis always has some element of planning in it. But the planning should never be too rigid. Because, in fact, the specific objective which the synthetic chemist uses as the excuse for his activity is often not of special importance in the general sense; rather, the important things are those that he finds out in the course of attempting to reach his objective. R. B. Woodward, Proc. Robert A. Welch Foundation Conf. Chem. Res. 1969, 12,3 When we have been faced with a problem of effecting a chemical synthesis we have sought known methods. We have not paused to think why we do not invent a new method every time. If we adopt this philosophy we are going to be extremely busy till the end of the century. Sir Derek H. R. Barton, Chem. Br. 1973, 9, 149

18. Nanopesticides (10 -9 m, a billionth of a meter) Urgent need of efficient agrochemicals - global population will reach 10 billion by 2050 . Traditional Pesticides such as   neonicotinoids (25% global agrochemical market) indiscriminately impact essential wildlife (bees). Bind to nicotinic receptors in the insect CNS meant for Ach NT, leading to overstimulation, and blocking of receptors followed by paralysis and death.

19. Nano-formulated pesticides can deliver active ingredients where they are needed without polluting the environment and without contaminating the plant surface/flowers etc. The major benefits of these nanoparticles includes the  improved solubility of active ingredients , better stability of formulation , slow release of active ingredient and improvement in mobility caused by smaller particle size and higher surface area . A good understanding of nano -materials is essential to overcome potential risks such as environmental hazards! How would nano formulations benefit?

20. 2. Enantioselective organocatalysis The idea of replacing expensive and unsustainable metal catalysts with small organic molecules has been very tempting for synthetic chemists. Organocatalysts are often more robust than their metal cousins, and some types – like sugars and amino acids – are easily available as single enantiomers.

21. The Nobel Prize in Chemistry 2021 was awarded jointly to Benjamin List and David W.C. MacMillan "for the development of asymmetric organocatalysis ." The Laureates’ seminal work in 2000 conceptualized the area of organocatalysis and stimulated its development. Today, organocatalysis constitutes the third pillar of catalysis, complementing biocatalysis and transition metal catalysis.

22. There are now  hundreds of enantioselective organocatalytic reactions  – from proline-catalysed aldol reactions to the Shi epoxidation , which uses a modified fructose catalyst. (Nature’s Chiral Pool)

23. L- Proline /S- Proline Enantiomerically Enriched/pure Enantioselective

24. Donor Acceptor a a b b New C-C bond Enamine ENAMINE MEDIATED ORGANOCATALYSIS

25. ENAMINE ORGANOCATALYSIS: HIGH ENANTIOSELECTIVITY

26. The Enamine catalysis: Aldol vs Mannich reaction Iminium cation Enamine Donor Acceptor X = O ) Iminium cation Chiral AA Aldol product X = O X = NH/R, Mannich product Acceptor (X = NH/R)

27. Enantioselective Organocatalysis : Iminium ion catalysis Lewis acid activation/ iminium ion activation leads to LUMO lowering LUMO Acceptor HOMO HOMO Donor LUMO LUMO Acceptor-EWG HOMO Donor-EDG LUMO HOMO When electron density is added to the molecule, it becomes easy to remove electrons ( HOMO raising ). When electron density is removed, it becomes more easy to add electrons (LUMO lowering). Electrons are always removed from the HOMOs of the donor and are added to LUMOs of the acceptor. Chiral

28. Five considerations: Expected to form only (E) geometry to avoid non-bonding interactions between the substrate double bond and the gem di-Me groups. The benzyl group would shield the Si face leaving Re face exposed for enantioselective bond formation. Was found good in Diels-Alder, nitrone addition, Fridel -craft alkylation, but was less reactive in indoles or furans were used in similar conjugate reactions. Reduced reactivity towards iminium ion formation. Second-generation cats was required and were designed. First-Generation MacMillan catalyst Participating lone pair is positioned adjacent To the Eclipsing ( cis ) Me, reducing reactivity of N towards iminium ion formation Si E vs Z geometry

29. Example 1 Diels-Alder Reactions

30. Second-Generation MacMillan catalyst Rapid formation of iminium ion. Replacing cis -Me group with ter t -butyl gave increased iminium geometry control and provided better coverage of the enantiotopic Si face leaving Re face more exposed. Could be used in broad range of transformations. Second-Generation First-Generation

31. 3. Solid-state batteries An excellent  battery technology that uses solid electrodes and a solid electrolyte, instead of the liquid or polymer gel electrolytes found in lithium-ion or lithium polymer batteries They are lighter, perform better at high temperatures, store more energy and aren’t flammable – outperform lithium ion batteries.  

32. The Li-ion battery has a risk of battery damage such as swelling caused by temperature change or leakage caused by external force since it uses liquid electrolyte solution.  A solid-state battery shows improved stability due to solid structure. The Li-ion battery, has a separator that keeps cathode and anode apart, with liquid electrolyte solution. On the other hand, the solid-state battery uses solid electrolyte, which also plays a role of a separator.  

33. 4. Flow chemistry Reaction components are pumped together at a mixing junction and flowed down a temperature-controlled pipe or tube. Continuous process. Faster reactions, cleaner products, Safer reactions, Easy optimization, Easy scaling up, Easy integration of reaction, work up and analysis (Jubilant Biosys ). Flow synthesis  a cheaper , higher yielding, less wasteful and often safer process than the batch production, both in the laboratory and on an industrial scale. Good for automation , allows running  thousands of reactions a day. Combining continuous flow chemistry and polymer synthesis  have produced compounds that were hard to make in a flask .

34. The Syrris Asia Flow Chemistry System in use in a laboratory

35. 5. Mechanochemistry Mechanochemistry – inducing reactions through mechanical forces – sometimes makes processes possible that are hard to do by traditional solution synthesis. Mechanochemistry refers to unusual chemical reactions induced by mechanical energy at room temperatures. Being a solution-free, it is energy saving, high-productivity and low-temperature process. However , there is limited understanding of the mechanochemical process because mechanochemistry is often conducted using closed milling devices, which are often regarded as a black box. 

36. 6 MOFs Gas separation, catalysis, carbon capture – metal–organic frameworks might be able to do it all. MOFs have already made it into commercial products like gas storage. These are sponge-like materials able to capture water from air, even in humidity as low as 20%.

37. 7. Directed enzyme evolution Directed evolution of enzymes  (Lab evolved enzymes) tailors them to catalyze new reactions, which are not possible with natural enzymes. No natural enzyme makes  carbon–silicon bonds  or  highly strained carbocycles . And while these molecules can also be made by traditional synthesis, it might involve costly or dangerous reagents. A lot of work needs to be done to realize the fullest potential of the Directed enzyme evolution. The Royal Swedish Academy of Sciences has decided to award the Nobel Prize for Chemistry 2018 with one half to Frances H Arnold “for the directed evolution of enzymes”, and the other half jointly to George P Smith and Sir Gregory P Winter "for the phage display of peptides and antibodies”.

38. 1. Random mutations are introduced in the gene of the enzyme to be changed DNA Mutation 2. The genes are inserted in bacteria, which use them as templates and produce randomly mutated enzymes Mutated enzymes Mutation 3. The modified enzymes are tested. The most efficient ones are identified. Discarded enzyme Test plate 4. New random mutations are introduced in the genes for the selected enzymes. The cycle begins again.

39. 8. Turning polymers back into monomers To stem the growing tide of unrecycled plastics, scientists have long been looking for ways to  break polymers down into their monomers . Intense research efforts have been focused on  plastics that break down naturally in the environment  as well as processes to reclaim common polymers. Chemists have even found  plastic-eating microbes . But for now, the raw material for making plastics – crude oil – is still so cheap that no recycling process can compete, though that might change in the future.

40. 9. Organic electronics The use of organic materials to build electronic devices may offer a more eco-friendly and affordable approach to the electronic world. Moreover , and more importantly, organic small molecules, polymers, and other materials afford electronic structures with unique properties, impossible to obtain with silicon based electronic. OLED lighting Solar cells Flexible displays Market forecast 2027 (source IDTechEx ): over $ 330 billion market RFID tags Electro-optics/ Photonics: NLO Motivation! Structure diversity, Low cost, flexible, light weight and environment-friendly, ease in processability

41. 10. 3D bioprinting The most fascinating discovery would be to see medical implants or entire organs being printed out of living cells. Researchers have already printed bones, blood vessels, trachea and cartilage structures . While entire organs remain out of reach, large companies like L’Oreal, BASF and Procter & Gamble are investing large sums in skin bioprinting  for creating skin grafts out of a patient’s own cells.

42. Bioprinting is an additive manufacturing process where biomaterials such as cells and growth factors are combined to create tissue-like structures that imitate natural tissues. The technology uses a material known as  bioink  to create these structures in a layer-by-layer manner.  This is one of the future technologies that would be used for production of tissues for use in reconstruction and regeneration.

43. Thanks