Structure of penicillin Adding to the core Chemistry itself Commentary

Dorothy Hodgkin pharmacology

Structure of penicillin

• To use X-rays to determine
• the atomic and molecular
• structure of a molecule,
• the molecule is purified
• and crystallized, sometimes
• difficult to do.
• It’s put in cryogenic helium,
• placed in a goniometer,
• and illuminated at several angles
• by a monochromatic beam of X-rays,
• each of which produces
• a two-dimensional image
• of the defraction pattern,
• leading to a three-dimensional map
• of electron density.
• Electron density and distribution
• and chemical information
• help scientists determine
• the structure of a molecule.
• Dorothy Hodgkin deduced
• the structure of penicillin,
• showing that it has
• a four-membered beta-lactam ring,
• which had not been expected,
• fused to a five-membered thiazolidine ring.
• The beta-lactam ring
• is responsible for penicillin’s
• antibacterial activity.

Adding to the core

• To the core structure of penicillin
• the form that Alexander Fleming found
• adds a benzyl group, making benzylpenicillin.
• Other forms of penicillin
• add other groups to the core, such as
• procaine benzylpenicillin,
• benzathine benzylpenicillin,
• and phenoxymethylpenicillin.
• The core, also called 6-APA
• or 6-Aminopenicillanic acid,
• is the base of several semisynthetic
• antibiotics that provide
• better bioavailability,
• broader spectrum of protection,
• increased stability,
• and are more tolerated by patients.
• Ampicillin, flucloxacillin,
• dicloxacillin, and methicillin,
• carbenicillin, ticarcillin, and piperacillin,
• and cephalosporin.

Chemistry itself

• By itself, chemistry
• tells a chemist
• what’s in it,
• but not how its pieces
• fit together.
• Chemistry doesn’t
• say where its pieces
• come from, or
• how they meet
• in this improbable
• existence.