OUTLINES OF PHYSIOLOGICAL CHEMISTRY
CONTENTS 1 INTRODUCTION 1 1 EARLY REVIEWS, CURRENT OBJECTIVES 1 2 BACKGROUND 2 EARLY SCIENTI? C INVESTIGATIONS 2 1 ADVANCES IN THE 18TH CENTURY 2 2 COLOR DIAGNOSTICS 2 3 EMERGENCE OF A NEW ANALYTICAL METHODOLOGY: QUANTITATIVE COMBUSTION ANALYSIS 2 4 EARLY 19TH CENTURY PIGMENT SEPARATION FROM BILE AND GALLSTONES 2 5 BILIRUBIN AND BILIVERDIN SEPARATION FROM BILE BY THE MIDDLE 19TH CENTURY 2 6 BILE PIGMENTS FROM GALLSTONES AND URINE, AND THEIR COMBUSTION ANALYSES DURING THE LATE 18TH TO MID-19TH CENTURIES 2 7 BILE PIGMENTS FROM GALLSTONES IN THE MIDDLE OF THE 19TH CENTURY 2 8 HÄMATOIDIN, BILIFULVIN, AND THE ORIGIN OF BILE PIGMENTS 2 9 BILE PIGMENT ISOLATION, PURI? CATION, AND COMBUSTION ANALYSIS IN THE 1860S AND 1880S 2 9 1 GEORG ANDREAS KARL STÄDELER GIVES THE NAME BILIRUBIN AS A FIRST STEP IS TAKEN TOWARD STRUCTURE IDENTI? CATION 2 9 2 JOHANN LUDWIG WILHELM (AKA JOHN LEWIS WILLIAM) THUDICHUM AND BILIRUBIN 2 9 3 RICHARD L MALY AND BILIRUBIN 2 10 THE EMERGENCE OF BILE PIGMENT SPECTROSCOPY: COLORIMETRY AND ITS APPLICATIONS 2 11 BILIRUBIN POLEMICS OF THE 1870S 2 12 CONJECTURAL CHEMISTRY AND BILIRUBIN POLEMICS AT THE CLOSE OF THE 19TH CENTURY 2 13 KNOWLEDGE OF BILIRUBIN NEAR THE END OF THE 19TH CENTURY 3 ADVENT OF THE BILIRUBIN STRUCTURE PROOF 3 1 EXPERIMENTALLY DERIVED MOLECULAR WEIGHT OF BILIRUBIN AT THE END OF THE 19TH CENTURY 3 2 BILIRUBIN ELEMENTAL COMBUSTION ANALYSES AND MOLECULAR WEIGHT DETERMINATIONS AT THE BEGINNING OF THE 20TH CENTURY 3 3 MOLECULAR FRAGMENTATION: INITIAL APPROACH TO BILIRUBIN STRUCTURE 3 4 KÜSTER’S MALEIMIDES AND NENCKI’S HÄMOPYRROL 4 A MODERN PROOF OF BILIRUBIN STRUCTURE EMERGES 4 1 OSKAR PILOTY AND THE STRUCTURE OF BILIRUBIN 4 2 HANS FISCHER AND THE EARLY STRUCTURES OF BILIRUBIN 4 2 1 FISCHER AND PILOTY CLEAVE BILIRUBIN IN HALF, 1912-1913 4 2 2 THE PILOTY-FISCHER POLEMICS 4 2 3 FISCHER’S BILIRUBINSÄURE, XANTHOBILIRUBINSÄURE, AND BILIRUBIN STRUCTURES CA 1914 4 2 4 THE ALKYLATED MONOPYRROLE COMPONENTS OF BILIRUBINSÄURE AND XANTHOBILIRUBINSÄURE 4 2 5 THE MONOPYRROLE PROPIONIC ACID COMPONENTS OF BILIRUBINSÄURE AND XANTHOBILIRUBINSÄURE 4 3 STATUS AND CONJECTURES REGARDING BILIRUBIN AND HEMIN STRUCTURES CIRCA 1916 4 4 RAISON D’ÊTRE BEHIND FISCHER’S FAILED TETRAPYRROLE STRUCTURES PRIOR TO 1926 5 PREPARING THE WAY TO THE CONSTITUTIONAL STRUCTURE OF BILIRUBIN 5 1 EVOLUTION OF THE BILIRUBIN STRUCTURE IN THE 1920S 5 2 TETRAPYRRYLETHYLENE-BASED HEMIN AND BILIRUBIN KAPUT 5 3 KÜSTER-FISCHER POLEMICS 5 4 SCHUMM-FISCHER POLEMICS 5 5 VINDICATION OF THE MACROCYCLIC PORPHYRIN STRUCTURE 5 6 THE STRUCTURE OF BILIRUBIN REFORMULATED 6 THE STATUS OF BILIRUBIN IN 1930 6 1 THE FISCHER LABORATORY IN THE 1930S AND THE STRUCTURE OF BILIRUBIN 6 2 SERENDIPITOUS DISCOVERY OF NEW DIPYRROLE FRAGMENTS OF MESOBILIRUBIN: NEOBILIRUBINSÄURE AND NEOXANTHOBILIRUBINSÄURE 6 2 1 SYNTHETIC DIPYRROLES, TETRAPYRROLES, INHOMOGENEITY, AND NEFARIOUS MIXTURE MELTING POINTS 6 2 2 A MAJOR BREAKTHROUGH IN UNDERSTANDING THE STRUCTURE OF BILIRUBIN RESOLUTION OF DISCORDANT MELTING POINTS AND SYNTHESIS OF MESOBILIRUBIN 6 2 3 THE STRUCTURE OF NATURAL-ANALYTICAL MESOBILIRUBIN CON? RMED SYNTHESIS OF MESOBILIRUBIN-IXA 6 3 FISCHER SOLVES THE STRUCTURE OF BILIRUBIN 6 3 1 DER NITRITKÖRPER 6 3 2 THE EXO-VINYL GROUP OF BILIRUBIN 6 3 3 BILIRUBIN STRUCTURE PROOF AND TOTAL SYNTHESIS QED 6 4 HANS FISCHER, FINIS VITAE 7 EVOLUTION OF THE CONSTITUTIONAL AND STEREOCHEMICAL STRUCTURE OF BILIRUBIN 7 1 LACTIM OR LACTAM TAUTOMERIC STRUCTURE? 7 2 CON? GURATION AT THE EXOCYCLIC DOUBLE BONDS 7 3 PROPOSING AND DETECTING HYDROGEN BONDS 8 ANALYSIS OF BILIRUBIN IN THREE DIMENSIONS 8 1 CHIRALITY CONSIDERATIONS 8 2 BILIRUBIN AS A CHIRAL MOLECULE 8 3 BILIRUBIN CONFORMATIONAL DYNAMICS BY NMR SPECTROSCOPY 8 4 CONFORMATIONAL DYNAMICS BY MOLECULAR MECHANICS COMPUTATION 8 5 BILIRUBIN CHIRALITY REVISITED CHIRAL DISCRIMINATION AND OPTICAL ACTIVITY 8 5 1 BILIRUBIN CIRCULAR DICHROISM FROM A FIRST-ORDER ASYMMETRIC TRANSFORMATION 8 5 2 BILIRUBIN AS A MOLECULAR EXCITON ABSOLUTE CON? GURATION FROM EXCITON CHIRALITY 8 5 3 MAPPING BILIRUBIN CONFORMATION TO EXCITON CHIRALITY CD 8 5 4 STEREOCONTROL OF BILIRUBIN CONFORMATIONAL ENANTIOMERISM BY INTRAMOLECULAR BUTTRESSING 9 UNDERSTANDING AND TRANSLATING BILIRUBIN STRUCTURE 9 1 BILIRUBIN CHEMISTRY REAWAKENED THANKS TO JAUNDICE PHOTOTHERAPY 9 2 HOW PHOTOTHERAPY EXPOSED BILIRUBIN (E)-CON? GURATION ISOMERS 9 2 1 (4Z,15E)- AND (4E,15Z)-BILIRUBIN DIASTEREOMERS (PHOTOBILIRUBIN) 9 2 2 LUMIRUBIN AND ISOBILIRUBIN DIASTEREOMERS 9 2 3 (E)-CON? GURATION BILIRUBINS FROM X-RAY CRYSTALLOGRAPHY 9 3 THE GLUE THAT BINDS PERSISTENCE, RECOGNITION, AND ROLE OF HYDROGEN BONDS 9 3 1 UNDERSTANDING DIPYRRINONE-CARBOXYLIC ACID HYDROGEN BONDING 9 3 2 MISCONCEPTIONS ABOUT HYDROGEN BONDING 9 3 3 INTRAMOLECULAR HYDROGEN BONDS AND PKA UN CORDON SANITAIRE? 9 4 EXTRAPOLATING FROM BILE PIGMENT STEREOCHEMISTRY AND HYDROGEN BONDING TO SYNTHETIC BILIRUBINOIDS 10 BILIRUBIN QUOD ERAT FACIENDUM 11 TRANSLATIONS 11 1 TRANSLATIONS TO SECTION 2 11 2 TRANSLATIONS TO SECTION 3 11 3 TRANSLATIONS TO SECTION 4 11 4 TRANSLATIONS TO SECTION 5 11 5 TRANSLATIONS TO SECTION 6 11 6 TRANSLATIONS TO SECTION 7 11 7 TRANSLATIONS TO SECTION 9 REFERENCES