THE CHEMISTRY OF VEGETABLE AND ANIMAL PHYSIOLOGY

By STEVEN WILLIAMS

CONTENTS 1 INTRODUCTION 11 EARLY REVIEWS, CURRENT OBJECTIVES 12 BACKGROUND 2 EARLY SCIENTI? C INVESTIGATIONS 21 ADVANCES IN THE 18TH CENTURY 22 COLOR DIAGNOSTICS 23 EMERGENCE OF A NEW ANALYTICAL METHODOLOGY: QUANTITATIVE COMBUSTION ANALYSIS 24 EARLY 19TH CENTURY PIGMENT SEPARATION FROM BILE AND GALLSTONES 25 BILIRUBIN AND BILIVERDIN SEPARATION FROM BILE BY THE MIDDLE 19TH CENTURY 26 BILE PIGMENTS FROM GALLSTONES AND URINE, AND THEIR COMBUSTION ANALYSES DURING THE LATE 18TH TO MID-19TH CENTURIES 27 BILE PIGMENTS FROM GALLSTONES IN THE MIDDLE OF THE 19TH CENTURY 28 HÄMATOIDIN, BILIFULVIN, AND THE ORIGIN OF BILE PIGMENTS 29 BILE PIGMENT ISOLATION, PURI? CATION, AND COMBUSTION ANALYSIS IN THE 1860S AND 1880S 291 GEORG ANDREAS KARL STÄDELER GIVES THE NAME BILIRUBIN AS A FIRST STEP IS TAKEN TOWARD STRUCTURE IDENTI? CATION 292 JOHANN LUDWIG WILHELM (AKA JOHN LEWIS WILLIAM) THUDICHUM AND BILIRUBIN 293 RICHARD L MALY AND BILIRUBIN 210 THE EMERGENCE OF BILE PIGMENT SPECTROSCOPY: COLORIMETRY AND ITS APPLICATIONS 211 BILIRUBIN POLEMICS OF THE 1870S 212 CONJECTURAL CHEMISTRY AND BILIRUBIN POLEMICS AT THE CLOSE OF THE 19TH CENTURY 213 KNOWLEDGE OF BILIRUBIN NEAR THE END OF THE 19TH CENTURY 3 ADVENT OF THE BILIRUBIN STRUCTURE PROOF 31 EXPERIMENTALLY DERIVED MOLECULAR WEIGHT OF BILIRUBIN AT THE END OF THE 19TH CENTURY 32 BILIRUBIN ELEMENTAL COMBUSTION ANALYSES AND MOLECULAR WEIGHT DETERMINATIONS AT THE BEGINNING OF THE 20TH CENTURY 33 MOLECULAR FRAGMENTATION: INITIAL APPROACH TO BILIRUBIN STRUCTURE 34 KÜSTER’S MALEIMIDES AND NENCKI’S HÄMOPYRROL 4 A MODERN PROOF OF BILIRUBIN STRUCTURE EMERGES 41 OSKAR PILOTY AND THE STRUCTURE OF BILIRUBIN 42 HANS FISCHER AND THE EARLY STRUCTURES OF BILIRUBIN 421 FISCHER AND PILOTY CLEAVE BILIRUBIN IN HALF, 1912-1913 422 THE PILOTY-FISCHER POLEMICS 423 FISCHER’S BILIRUBINSÄURE, XANTHOBILIRUBINSÄURE, AND BILIRUBIN STRUCTURES CA 424 THE ALKYLATED MONOPYRROLE COMPONENTS OF BILIRUBINSÄURE AND XANTHOBILIRUBINSÄURE 425 THE MONOPYRROLE PROPIONIC ACID COMPONENTS OF BILIRUBINSÄURE AND XANTHOBILIRUBINSÄURE 43 STATUS AND CONJECTURES REGARDING BILIRUBIN AND HEMIN STRUCTURES CIRCA 44 RAISON D’ÊTRE BEHIND FISCHER’S FAILED TETRAPYRROLE STRUCTURES PRIOR TO 5 PREPARING THE WAY TO THE CONSTITUTIONAL STRUCTURE OF BILIRUBIN 51 EVOLUTION OF THE BILIRUBIN STRUCTURE IN THE 1920S 52 TETRAPYRRYLETHYLENE-BASED HEMIN AND BILIRUBIN KAPUT 53 KÜSTER-FISCHER POLEMICS 54 SCHUMM-FISCHER POLEMICS 55 VINDICATION OF THE MACROCYCLIC PORPHYRIN STRUCTURE 56 THE STRUCTURE OF BILIRUBIN REFORMULATED 6 THE STATUS OF BILIRUBIN IN 61 THE FISCHER LABORATORY IN THE 1930S AND THE STRUCTURE OF BILIRUBIN 62 SERENDIPITOUS DISCOVERY OF NEW DIPYRROLE FRAGMENTS OF MESOBILIRUBIN: NEOBILIRUBINSÄURE AND NEOXANTHOBILIRUBINSÄURE 621 SYNTHETIC DIPYRROLES, TETRAPYRROLES, INHOMOGENEITY, AND NEFARIOUS MIXTURE MELTING POINTS 622 A MAJOR BREAKTHROUGH IN UNDERSTANDING THE STRUCTURE OF BILIRUBIN RESOLUTION OF DISCORDANT MELTING POINTS AND SYNTHESIS OF MESOBILIRUBIN 623 THE STRUCTURE OF NATURAL-ANALYTICAL MESOBILIRUBIN CON? RMED SYNTHESIS OF MESOBILIRUBIN-IXA 63 FISCHER SOLVES THE STRUCTURE OF BILIRUBIN 631 DER NITRITKÖRPER 632 THE EXO-VINYL GROUP OF BILIRUBIN 633 BILIRUBIN STRUCTURE PROOF AND TOTAL SYNTHESIS QED 64 HANS FISCHER, FINIS VITAE 7 EVOLUTION OF THE CONSTITUTIONAL AND STEREOCHEMICAL STRUCTURE OF BILIRUBIN 71 LACTIM OR LACTAM TAUTOMERIC STRUCTURE? 72 CON? GURATION AT THE EXOCYCLIC DOUBLE BONDS 73 PROPOSING AND DETECTING HYDROGEN BONDS 8 ANALYSIS OF BILIRUBIN IN THREE DIMENSIONS 81 CHIRALITY CONSIDERATIONS 82 BILIRUBIN AS A CHIRAL MOLECULE 83 BILIRUBIN CONFORMATIONAL DYNAMICS BY NMR SPECTROSCOPY 84 CONFORMATIONAL DYNAMICS BY MOLECULAR MECHANICS COMPUTATION 85 BILIRUBIN CHIRALITY REVISITED CHIRAL DISCRIMINATION AND OPTICAL ACTIVITY 851 BILIRUBIN CIRCULAR DICHROISM FROM A FIRST-ORDER ASYMMETRIC TRANSFORMATION 852 BILIRUBIN AS A MOLECULAR EXCITON ABSOLUTE CON? GURATION FROM EXCITON CHIRALITY 853 MAPPING BILIRUBIN CONFORMATION TO EXCITON CHIRALITY CD 854 STEREOCONTROL OF BILIRUBIN CONFORMATIONAL ENANTIOMERISM BY INTRAMOLECULAR BUTTRESSING 9 UNDERSTANDING AND TRANSLATING BILIRUBIN STRUCTURE 91 BILIRUBIN CHEMISTRY REAWAKENED THANKS TO JAUNDICE PHOTOTHERAPY 92 HOW PHOTOTHERAPY EXPOSED BILIRUBIN (E)-CON? GURATION ISOMERS 921 (4Z,15E)- AND (4E,15Z)-BILIRUBIN DIASTEREOMERS (PHOTOBILIRUBIN) 922 LUMIRUBIN AND ISOBILIRUBIN DIASTEREOMERS 923 (E)-CON? GURATION BILIRUBINS FROM X-RAY CRYSTALLOGRAPHY 93 THE GLUE THAT BINDS PERSISTENCE, RECOGNITION, AND ROLE OF HYDROGEN BONDS 931 UNDERSTANDING DIPYRRINONE-CARBOXYLIC ACID HYDROGEN BONDING 932 MISCONCEPTIONS ABOUT HYDROGEN BONDING 933 INTRAMOLECULAR HYDROGEN BONDS AND PKA UN CORDON SANITAIRE? 94 EXTRAPOLATING FROM BILE PIGMENT STEREOCHEMISTRY AND HYDROGEN BONDING TO SYNTHETIC BILIRUBINOIDS 10 BILIRUBIN QUOD ERAT FACIENDUM 11 TRANSLATIONS 111 TRANSLATIONS TO SECTION 112 TRANSLATIONS TO SECTION 113 TRANSLATIONS TO SECTION 114 TRANSLATIONS TO SECTION 115 TRANSLATIONS TO SECTION 116 TRANSLATIONS TO SECTION 117 TRANSLATIONS TO SECTION REFERENCES