Penicillin

choi

When posting "Ocular Syphilis" two days ago, I forgot to attach text of the article, which is done today.
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(1) Penicillin contains a four-membered β-Lactam.

Etymologia: β-Lactamase. Emerging Infectious Disease, 22: 1689 (2016)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994330/
(" 'Lactam' is a portmanteau of 'lactone' (from the Latin lactis, 'milk,' since lactic acid was isolated from soured milk) and 'amide' ")
(a) Pay attention to where β-lactamase cleaves the β-lactam ring.
(b) lactone
https://en.wikipedia.org/wiki/Lactone
("Lactones are cyclic carboxylic esters * * * formed by intramolecular esterification of the corresponding hydroxycarboxylic acids, which takes place spontaneously when the ring that is formed is five- or six-membered")
(c) Lactam
https://en.wikipedia.org/wiki/Lactam
(section 1 Nomenclature)
is different from latone, because N in the former replaces O in the latter. That is what they are called lactam and lactone, respectively.

(2) chemical structure of penicillin:
(a) penicillin
https://en.wikipedia.org/wiki/Penicillin
(structure at the upper right corner: In penicillin G, the R is benzyl (phenyl-CH2- ), whereas in penicillin V, the R is phenoxymethyl (phenyl-O-CH2- ).
(b) penicillin G
https://pubchem.ncbi.nlm.nih.gov/compound/Penicillin-g
("The bactericidal activity of penicillin G results from the inhibition of cell wall synthesis and is mediated through penicillin G binding to penicillin binding proteins (PBPs). * * * Oral absorption in fasting, healthy humans is only about 15-30% as it is very susceptible to acid-catalyzed hydrolysis")

Target of penicillin, penicillin binding proteins (PBPs) of bacteria is needed to make bacterial cell wall.

(3) Why were they called penicillin G or V?
(a) history of penicillin
https://en.wikipedia.org/wiki/History_of_penicillin
(section 3 The breakthrough discovery, section 3.5 Reception and publication;

, where footnote 95 (mentioned in section 7) is:
Chemistry of Penicillin. Science, 102: 627 (1945)
https://science.sciencemag.org/content/102/2660/627
(first page only)
is how penicillin G got its name. I suspect that penicillin G was so named, because it was identified as the second penicillin. See
Celia Henry Arnaud, Penicillin. C&EN volume 83 (June 20, 2005)
https://cen.acs.org/articles/83/i25/Penicillin.html
("In 1943, a surprising bit of information was revealed by purification studies in Britain and the US: There isn't just one penicillin. Elemental analysis indicated that the groups were working with compounds with slightly different compositions. They had a common core but different side chains. The British researchers, who produced penicillin with surface fermentation, were working with penicillin F, now known to be 2-pentenylpenicillin. In contrast, the Americans were working with penicillin G, or benzylpenicillin")
(c) "Like most natural products, penicillin is present in Penicillium moulds as a mixture of active constituents * * * The precise constitution of the penicillin extracted depends on the species of Penicillium mould used and on the nutrient media used to culture the mould.[6] Fleming's original strain of Penicillium rubens produces principally penicillin F, named after Fleming. But penicillin F is unstable, difficult to isolate, and produced by the mould in small quantities."  en.wikipedia.org for penicillin (section 1 Nomenclature).

(4)
(a) phenoxymethylpenicillin
https://en.wikipedia.org/wiki/Phenoxymethylpenicillin
(section 5 History, section 6 Names: "Penicillin V was named 'V' for Vertraulich (confidential)" )
(i) German-English dictionary:
* vertraulich (adj; [verb] vertrauen [to trust, to place confidence in] +‎ -lich [an adjectival suffix] ): "confidential"
https://en.wiktionary.org/wiki/vertraulich
(ii) The German or Jewish (Ashkenazic) surname Ehrlich is from an adjective of the same spelling that means "honest."
https://en.wiktionary.org/wiki/ehrlich
(b) David Greenwood (emeritus professor of Antimicrobial Science University of Nottingham medical school), Antimicrobial Drugs; Chronicle of a twentieth century medical triumph. Oxford University Press (2008) at pages 120-121
https://books.google.com/books?i ... amp;ved=2ahUKEwi6mI
("Towards the end of 1951 * * * a company [Biochemie GmbH, based in Kundl, Austria -- a town of 4,464 on Jan 1, 2018 per en.wikipedia.org] biologist, Ernest Brandl was charged with the task of solving persistent problems with contamination [by bacteria] in the penicillin fermentation tanks. The difficulty was to inhibit growth of the contaminant micro-organism without interfering with the Penicillium mould. Various conventional antibacterial substances were tested without success and with more hope than expectation, he tried adding phenoxyethanol to the fermentation broth. To his surprise, Brandl found that this stimulated an increased yield of penicillin. A young company colleague, the chemist Hans Margreiter was brought in to investigate the phenomenon. He discovered that the product of fermentation was not conventional benzylpenicillin since it was stable to hydrolysis by acids. He postulated that the alcohol Brandl had used was transformed to phenoxyacetic acid in place of phenylacetic acid, the precursor used in benzylpenicillin manufacture, the product obtained was phenoxymethylpenicillin ([footnote] 79). Brandl and Margteiter realized that they had stumbled on something unexpected an possibly important: a form o penicillin that was not broken down in the acid conditions of the stomach and which could therefore be administered orally. The new penicillin became known in the company as penicillin V -- 'V' for vertraulich (confidential)" )

(5) For determining the chemical structure of penicillin in 1945 by using crystallography, Dorothy Crowfoot Hodgkin alone was awarded Nobel prize in chemistry in 1964.
https://www.nobelprize.org/prizes/chemistry/1964/perspectives/
("Victory in Europe Day in [University of] Oxford, 8 May 1945. * * * Hodgkin had just solved the structure of penicillin [that day] * * * Five years earlier, on a morning in May 1940, Hodgkin had bumped into an unusually animated Chain outside the Dunn School of Pathology. Chain told Hodgkin that he and his colleague Howard Florey had just discovered something amazing. Florey and Chain were experimenting with penicillin, the bacteria-killing substance that Alexander Fleming had somewhat fortuitously discovered in moulds in 1928. Since Fleming’s discovery, several researchers tried and failed to purify active forms of penicillin, and had resigned themselves to the fact that penicillin might be interesting to the bacteriologist but would be of no great practical importance in medicine, until the experiment that Chain was so excited about.  Florey and Chain had injected eight mice with lethal doses of bacteria, but four of them also received extracts of penicillin. The untreated mice died within one day, but to Florey and Chain’s excitement the penicillin-treated mice survived for several days or weeks. For the first time since Fleming’s discovery it seemed possible that that penicillin extracts might be used as a remedy * * * Hodgkin started her own lab at Somerville College, Oxford, in 1935. Within a year she produced her first X-ray photograph of insulin, after which she is said to have wandered the streets of Oxford in a daze, until advised to go home by a kindly policeman in the early hours of the morning. * * * In February 1941, the first human patients were treated, and doctors witnessed resurrection-like cures of death-bound patients with relatively impure extracts. * * * It was not until July 1943 that they knew the composition of the active ingredient. After systematically breaking down penicillin into smaller pieces, chemists knew it consisted of 27 atoms: 11 hydrogen, 9 carbon, 4 oxygen, 2 nitrogen atoms and 1 sulphur atom. The trouble was that this combination of atoms could form two very different structures, and chemists couldn’t decide which structure was more likely. Some chemists were convinced the structure contained two five-membered rings connected by a single bond, known as a thiazolidine-oxazolone. Others were equally sure it was a four-membered ring fused to a five-membered ring, known as a beta lactam."_
(a) Victory in Europe Day
https://en.wikipedia.org/wiki/Victory_in_Europe_Day
("formal acceptance [on May 8, 1945] by the Allies of World War II of Germany's unconditional surrender" offered a day prior)
(b) About Us. Sir William Dunn School of Pathology.
https://www.path.ox.ac.uk/content/about-us-0   
("The Dunn School is a world-class biomedical research Department at the University of Oxford")
(c) insulin
https://en.wikipedia.org/wiki/Insulin
(i