Never let Reality get in the way of a good Hypothesis

Date : Today, Time : From seventeen minutes past one to three in the blessed afternoon,
Event : 11 (eleven, E-L-E-V-E-N, aagaaro, aekadosh, etc. ) salesmen, selling everything from soap
to electric chimneys to magnetic ear cleaners ( I still haven't figured the last one out - I mean, how can one have a magnetic ear cleaner ?!!), and on top of that there was this chap who was
trying to get me to donate some money "For the Enviroment" - I was understandably reluctant after noticing the "enviroment", but I still gave him some money, and then, he tells me that
he won't give me a receipt ! So, I took the money back and kicked him out ( the first part wasn't as easy as it sounds - I had to threaten him with the local crimi..police before he gave in ).Well, after this I decided to write something about nature - Here goes...

The Vatican holds a fresco by Raphael entitled The School of Athens. Plato and Aristotle stride toward us. Plato's hand points to the heavens, Aristotle's outward, along the plane of the earth. The message is consistent with their philosophies - whereas Plato had a geometric prototheory of the chemistry of matter, Aristotle described in reliable detail how Tyrian purple (now known to be a precursor of indigo) was extracted from rock murex snails. Plato searched for the ideal; Aristotle looked to nature.

Short note : Contrary to the ideas of my next door neighbours, who are ardent supporters of CPIM, and for all I know, the ideas of many others ( although I fervently hope that this is not
the case ), Plato is the name of a philosopher, or in some cases, a distinctive dark-floored large crater on the Moon just north of Mare Imbrium, NOT a local company that manufactures
plates.

Remarkably, science today faces the quandary that Raphael's fresco epitomized. Should it follow the hand sign of Aristotle or that of Plato? Can we, for example, hope to make better composites by mimicking the microstructure of a feather or of a strand of spider's silk? Are scientists better advised to seek their inspiration in ideal mathematical forms, in icosahedra and in footballs (soccer, not the... solidified crudity that is rugby )? Or should we hazard chance?

To many people ( mainly the businessmen whose companies have to pay extra for environmentally acceptable manufacturing methods ) the difference between what is natural and what is not, is arbitrary - humanity is a product of nature, and thus, so is anything produced by it. Such a view is understandable and has a lot history, but it does away with a distinction that troubles ordinary and thoughtful people. So I will not adopt it and instead will distinguish between the actions, mostly intended, of human beings and those of animals, plants and the inanimate world around us. A sunset is natural; a sulphuric acid factory is not. The one and a half billion odd head of cattle in this world pose an interesting problem for any definition. Most
of them are both natural and unnatural - the product of breeding controlled by humans.So, the first thing that we need to decide is the definition of "natural".

The molecules that exist "naturally" on the earth emerged over billions of years as rocks cooled, oceans formed, gases escaped and life evolved. The number of natural molecules is in the billions; perhaps a few hundred thousand have been separated, purified and identified. The vast majority of the compounds that fit into the "unnatural" category were created during the past three centuries. Chemists have added perhaps 20 million well-characterized molecules to nature's bounty.

To every thing of this world, be it living or not, there is structure. Deep down are molecules, persistent groupings of atoms associated with other atoms. There is water in the distilled form in the laboratory, in slightly dirty and acid snow, in the waters associated with our protein molecules. All are H2O. When chemistry was groping for understanding, there was a reasonable reluctance to merge the animate and inanimate worlds.
Friedrich W0hler convinced many people that the worlds were not separate by synthesizing, in 1828, organic urea from inorganic silver cyanate and ammonium chloride, but even today, we divide chemistry into Organic and Inorganic - admittedly, this is mostly for historical reasons ( "organic" chemistry has many molecules which have never existed, nor are likely to exist anywhere outside of a laboratory ), but organic chemistry, based mostly upon the compounds of Carbon holds a special
importance to most humans - it is what we are made of !!! It must be very special !

Many believe that there is some kind of special beauty in "nature" - there is beauty in everything, but most of us refuse to see it. This means that we see the beauty only in what is useful to us, except in the case where the object is "natural", which, for our purposes means "already exists". Primaxin is one of the most effective antibiotics on the market, a prime money-maker for Merck & Co. The pharmaceutical is not a single molecule but a designed mixture of two compounds, imipenem and cilastatin. These are their "trivial" names. The real names are a bit longer; for instance, imipenem is

[5R-[5a, 6a(R*)]]-6-(1-hydroxyethyl)-3-[[2-[(iminomethyl)amino]ethyl]thio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid.

The production of thienamycin required 21 major steps, each involving several physical operations: dissolution, heating, filtration, crystallization. Between the starting material - a common
amino acid, L-aspartic acid and the desired product hienamycin 20 other molecules were isolated and purified.
The first impression that one gets is of complexity. That intricacy is essential, a laboratory counterpoint to the biochemical complexity of bacteria and us. We would like there to be "magic bullets" of abiding simplicity. The real world is complicated and beautiful. We had better come to terms with that richness. To get a feeling for the sweat, if not the blood and tears, of the process, we need to turn to the experimental section of the paper reporting the synthesis. Here is an excerpt of that experimental protocol, describing a critical, inventive step in the synthesis, the transformation from compound 8 to 9:

A suspension of diazo keto ester 8 (3.98g, 10.58 mmol) and rhodium (II) acetate dimer (0.04 g, 0.09 mmol) in anhydrous toluene (250 mL) was thoroughly purged with nitrogen, and then heated with stirring in an oil bath maintained at 80oC. After heating for two hours, the reaction mixture was removed from the bath and filtered while warm through a pad of anhydrous magnesium sulphate. The filtrate was evaporated under vacuum to afford the bicyclic keto ester 9 (3.27 g, 89%) as an off-white solid.

You can be sure that this jargon-laden account of an experimental procedure is a sanitized, too linear narrative; it is the way things were at the end: neat, optimized. Not the way it first happened. Putting that aside, you feel work, a sequence of operations that take time and effort. Sometimes, just as in our romantic notions of words springing from the brow of inspired poets, we forget the sheer labour of creation.

You ( like me) might be interested to see the way these experimental procedures change when the very same process is scaled up. You can't make hundreds of millions of dollars' worth of
tienamycin the same way you make a few grams in the laboratory. Here is the description of the industrial synthesis, for the very same step:

The solids containing 200 kg of 8 are dropped into 476 gallons of MeCl2 in tank TA-1432. Meanwhile, the reactor ST-1510 is cleaned out by a 200-gallon MeCl2 boilout. The slurry is transferred to ST-1510, followed by a 50-gallon MeCl2 line flush. An additional 400 gallons of dry MeCl2 are added to ST-1510, and hot water (65oC) is applied to the jackets to concentrate the batch to 545 gallons where the slurry KF (Karl Fischer) is approximately 0.5 g/1 H2O. Distillates are condensed and collected in another tank.

Making veal stroganoff for a thousand people is not the same as cooking at home for four.

People think writing a intriguing story is difficult, that good poetry has to be inspired by something - so do I ; science, however, has been reduced to something less.. a handful of formulae, learnt by rote, synonymous with clinical - where is the appreciation of the beauty of science ? Where is the spirit of enquiry that drove people like Richard Feynman ?If people are able to see the beauty in , and buy "modern" paintings ( many of which, to me, at least, seem to have been drawn by drunk chimpanzees ), then why can they not see the same thing in the structure of th ferric wheel ?

Stephen J. Lippard and Kingsley L. Taft of the Massachusetts Institute of Technology synthesized the ferric wheel, also known as [Fe(OCH3)2(O2CCH2Cl)]10. They discovered this exquisite molecule while studying model molecules for inorganic reactions that occur in biological systems. For instance, a cluster of iron and oxygen atoms is at the core of several important proteins, such as hemerythrin, ribonucleotide reductase, methane monooxygenase and ferritin (not household words these, but essential to life). In the course of their broad attack on such compounds, Lippard and Taft performed a deceptively simple reaction. Just how simple it seems may be seen from their experimental section, reproduced in its entirety:

Compound 1 was prepared by allowing the monochloroacetate analogue of basic iron acetate, [Fe3O(O2CCH2Cl)6 (H2O)3](NO3) (0.315 g, 0.366 mmol), to react with 3 equiv of
Fe(NO3)3·9H2O (0.444 g, 1.10 mmol) in 65 mL of methanol. Diffusion of ether into the green-brown solution gave a yellow solution, from which both gold-brown crystals of 1 and a yellow
precipitate deposited after several days.

Using x-ray diffraction on the gold-brown crystals, Lippard and Taft determined the arrangement of atoms in the molecule. The structure consists of 10 ferric ions (iron in oxidation state three) in a near circular array. Each iron atom is joined to its neighbors by methoxide and carboxylate bridges, "forming a molecular ferric wheel," to quote its makers. No one will deny the visual beauty of this molecule. It does not have the half billion dollar annual sales of Primaxin, but nobody who has seen the molecule can disagree to its beauty, which is not just the inherent beauty born ot of symmetry, but, somehow, I know not how, is as beautiful as any tropical sunset - yet this is not a "natural" molecule. Perhaps some day the ferric wheel will find a use; perhaps it will form a link in explaining the function of iron-containing proteins. I do not really care - for me, this molecule is just that ; a molecule, a piece of matter, which somehow manages to be.. there is really no other word - beautiful.

Is this not part of nature ? Perhaps this is what the old philosophers meant when they spoke of an omnipresent God - the beauty around us, within us, the wondrous beauty that prevades existence itself; a French chemist, Alain Sevin, has put it well:

The incredible richness and fantasy of Nature is an act of defiance to Man, as if he had to do better in any domain. Flying faster than birds, diving deeper than whales.... We are Promethean characters in an endless play which now is in its molecular act.

We are driven to transform. We have learned to do it very well. But this play is not a comedy.

Were humanity in search of a single icon, the outstretched hand of Prometheus bringing fire to humanity would serve well. Prometheus, a name meaning "forethought," represents the element of design, the process of fruitfully taking advantage of chance creation. Fire is appropriate because it drives transformation. The hand of Prometheus is the symbol of creation - the hand of God reaching to Adam in Michelangelo's fresco, the hands in contentious debate in Durer's Christ among the Doctors, the infinite variety of hands that Rodin
sculpted. Hands bless, caress and hide, but most of all, they shape.

Mbwhjaja !!! This is getting too sentu and aantellectual ! Well, there you go, a nice, long post making up for my lack of updates.

Bye, Debayan Gupta.

P.S. : Comment. Or Else.
P.P.S.: Immature authors imitate. Mature authors steal.
P.P.P.S. : More of this essay in my next post.