PORPHYRINS AND METALLOPORPHYRINS A new edition based on the original volume by J. E. Falk Edited by KEVIN M. SMITH University of Liverpool ELSEVIER SCIENTIFIC PUBLISHING COMPANY AMSTERDAM - OXFORD - NEW YORK ELSEVIER SCIENTIFIC PUBLISHING COMPANY 335 Jan van Galenstraat P.O. Box 211, Amsterdam, The Netherlands AMERICAN ELSEVIER PUBLISHING COMPANY, INC. 52 Vanderbilt Avenue New York, New York 10017 Universe- - : Bibliothek - München ì Staatsbibliothenek Münch en Library of Congress (.'alalo^in^ in I 'ublkation Data Main entry under title: Porphyrins and metalloporphyrins. Ausgeschieden •Us den Beständen Includes bibliographical references and index. der BSß München 1. Porphyrins and porphyrin compounds. I. Falk, J. E. Porphyrins and metalloporphyrins. II. Smith, Kevin M. QD401.P7 1975 547'.593 75-20551 ISBN 0-444-41375-8 ISBN 0-444-41375-8 Copyright © 1975 by Elsevier Scientific Publishing Company, Amsterdam All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopy• ing, recording, or otherwise, without the prior written permission of the publisher, Elsevier Scientific Publishing Company, Jan van Galenstraat 335, Amsterdam Printed in The Netherlands PREFACE In 1964, J.E. Falk was able to give one man's view of the porphyrin and metalloporphyrin field at possibly the last time that such a major task was possible. Since then the area has mushroomed outwards and blossomed in a quite remarkable manner, and this may in no small way be due to the stimu• lus provided by the appearance of Porphyrins and Metalloporphyrins. Around the time of his death, Falk was addressing himself to the task of updating and revizing his highly successful book, ,and realizing the magnitude of the undertaking, had begun to gather about him varioiïs colleagues who might be willing to contribute to a multi-authored Secoq|| Edition. Alas, all of this came to nothing, but the demand for a new andexpanded edition of Falk remained. The present book represents an attempt by some of the leading authori• ties in the field to fill the gap left by the progress of porphyrin chemistry past the account written by Falk. It differs considerably from the original, mainly in size, but also in the organization of the chapters into eight sec• tions. A detailed description of the content of each section would be out of place 1ère, but it is worth commenting that sections dealing with synthetic and biological aspects have been added, as well as chapters dealing in depth with many spectroscopic methods which were only in their infancy in 1964. In the whole book Falk's 'systematic and rational exposition which would have been quite impossible some years ago' has been carried to the bounda• ries of present research. An attempt has been made to retain the idea of a 'Laboratory Handbook' which was the underlying concept in Falk. Though the book has grown dra• matically in siz&, a substantial section dealing with laboratory methods has been included.' Many of the procedures have not been noticeably im• proved since 1964, and in these cases there are few changes from the account written by Falk; however, in other respects, the Laboratory Methods Section has been expanded and revized. The manuscript deadline for the present book was 1st January 1975, and with the exception of a few chapters which arrived in late March 1975, literature published after December 1974 has not been considered. However, as always when accounts are written by active research workers in the field, the chapters contain abundant references to unpublished work, or work in press, as well as personal communications from other researchers. In order to preserve the timeliness of the contributions in this book, it was necessary to VI PREFACE proceed to publication without two manuscripts which were estimated, by the authors, to be one month or more from completion on 1st June 1975. It is a pleasure to record my thanks to Professor G.W. Kenner, F.R.S., for his advice and encouragement during the past two years. In contributed volumes of this type with about twenty chapters, crises arise at fairly regular intervals; I would like to thank Professor Dr J.W. Buchler (Aachen) and Dr J.-H. Fuhrhop (Stöckheim über Braunschweig) for unhesitating assistance during these difficult times, and for providing the encouragement to go ahead in the formative days of this project. Liverpool, June 1975 Kevin M. Smith CONTENTS Preface V SECTION A: GENERAL AND SYNTHETIC ASPECTS Chapter 1 General features of the structure and chemistry of porphyrin compounds Kevin M. Smith 1.1 Structures and nomenclature 3 1.1.1 Nomenclature 5 1.1.2 Related structures 6 1.1.2.1 Reduced porphyrin macrocycles 6 1.1.2.2 Oxidized porphyrin macrocycles 8 1.1.2.3 Porphyrin analogs 8 1.1.3 Isomerism in porphyrins 9 1.2 General chemistry 9 1.2.1 Aromaticity of the macrocycle 9 1.2.2 Tautomerism in the macrocycle 10 1.2.3 Ionization of porphyrins 11 1.2.3.1 Nitrogen atoms 11 1.2.3.2 Carboxylic acid side-chains 14 1.2.3.3 Acid (HCl) numbers 15 1.2.3.4 Complexation with metal ions 15 1.2.4 Stability of porphyrin compounds 15 1.2.4.1 General features 15 1.2.4.2 Instability to light 16 1.2.4.3 Other examples of instability 16 1.3 Occurrence of porphyrin compounds 16 1.3.1 Metal complexes 16 1.3.2 Metal-free porphyrins 18 1.4 Chromophores of porphyrin systems 19 1.4.1 Porphyrins 20 1.4.1.1 In neutral solvents 20 1.4.1.1.1 Etio type spectra 20 1.4.1.1.2 Rhodo type spectra 21 1.4.1.1.3 Oxorhodo type spectra 23 1.4.1.1.4 Phyllo type spectra 23 1.4.1.1.5 Spectra of porphyrins containing isocyclic rings 23 1.4.1.2 In acidic solvents 24 1.4.1.3 In alkaline solvents 24 Vili CONTENTS 1.4.2 Chlorins 25 1.4.3 Metalloporphyrins 25 1.4.4 Phlorins and oxophlorins 25 References 2 7 Chapter 2 Synthesis and preparation of porphyrin compounds Kevin M. Smith 2.1 Scope 29 2.2 Syntheses of dipyrrolic intermediates 30 2.2.1 Pyrromethenes 30 2.2.2 Pyrrome thanes 31 2.2.3 Pyrroketones 31 2.3 Syntheses of porphyrins 32 2.3.1 By polymerization of monopyrroles 32 2.3.2 From dipyrrolic intermediates 33 2.3.2.1 From pyrromethenes 33 2.3.2.2 From pyrromethanes 35 2.3.2.3 From pyrroketones 36 2.3.3 From open-chain tetrapyrrolic intermediates 36 2.3.3.1 From bilanes and oxobilanes 37 2.3.3.1.1 Using bilane intermediates 37 2.3.3.1.2 Using a-oxobilane intermediates 38 2.3.3.1.3 Using ò-oxobilane intermediates 40 2.3.3.2 From bilenes 41 2.3.3.2.1 Using l',8'-dimethyl-6-bilenes 41 2.3.3.2.2 Using 6-bilene-l',8'-diesters 42 2.3.3.2.3 Using other 6-bilenes 43 2.3.3.3 From a,c-biladienes 44 2.3.3.3.1 Using l',8'-dimethyl-a,c-biladienes 44 2.3.3.3.2 Using l'-bromo-8'-methyl-a,c-biladienes 46 2.3.3.3.3 Using other a,c-biladienes 46 2.3.4 General conclusions 47 2.4 Preparation of porphyrins by degradation of natural pigments 48 2.4.1 From hemoglobin 48 2.4.1.1 Protohemin 48 2.4.1.2 Hematoporphyrin-IX 49 2.4.1.3 Protoporphyrin-IX 49 2.4.1.4 Mesoporphyriri-IX 50 2.4.1.5 Deuteroporphyrin-IX and its derivatives 50 2.4.1.6 Coproporphyrin-III 51 2.4.1.7 Other porphyrins of biological significance 51 2.4.2 From the plant chlorophylls 52 References 55 SECTION B: BIOLOGICAL ASPECTS Chapter 3 Biosynthesis of porphyrins, chlorins, and corrins A.R. Battersby and E. McDonald 3.1 Introduction 61 3.2 The biosynthesis of porphobilinogen 62 CONTENTS IX 3.2.1 Historical background and fundamental studies 62 3.2.2 ALA synthetase 66 3.2.2.1 Mechanistic studies 66 3.2.2.1.1 Cofactor requirement 66 3.2.2.1.2 Binding and activation of glycine 68 3.2.2.1.3 Binding of succinyl coenzyme A and the acyla- tion step 70 3.2.2.1.4 The decarboxylation step 70 3.2.2.2 Inhibition of ALA synthetase in vivo 72 3.2.3 ALA dehydratase 7 2 3.2.3.1 Binding of ALA 73 3.3 Conversion of porphobilinogen into uroporphyrinogen-III 74 3.3.1 Porphyrinogens as biosynthetic intermediates 74 3.3.2 Outline of the problem 75 3.3.3 Porphobilinogen deaminase 77 3.3.4 Uroporphyrinogen-III cosynthetase 78 3.3.5 Enzymic formation of uroporphyrinogen-I 78 3.3.5.1 Stoichiometry 78 3.3.5.2 Intermediates 79 3.3.5.3 Possible mechanistic scheme 82 3.3.6 Enzymic formation of uroporphyrinogen-III 83 3.3.7 Analysis of hypotheses regarding formation of the type-Ill isomer 85 3.3.8 Basic studies with carbon-13 n.m.r. and integrity of the type-Ill macrocycle 87 13 3.3.9 Nature of the rearrangement process from experiments with C2-PBG 89 3.3.10 Enzymic studies with pyrromethanes 92 3.3.10.1 The AP • PA pyrromethane 92 3.3.10.2 The PA • PA pyrromethane 93 3.3.10.3 The AP • AP pyrromethane 93 3.3.10.4 The PA • AP pyrromethane 94 3.3.10.5 Conclusions 95 3.3.11 Enzymic studies with a tripyrrole and a bilane 96 3.3.12 Conclusions 96 3.4 Side-chain modifications and aromatization to protoporphyrin-IX 96 3.4.1 Decarboxylation of uroporphyrinogen-III 96 3.4.1.1 The partially decarboxylated intermediates 97 3.4.2 Oxidative decarboxylation of coproporphyrinogen-III 99 3.4.2.1 Enzymic studies 100 3.4.2.2 Mechanistic studies 101 3.4.2.3 Intermediates 102 3.4.3 Aromatization of protoporphyrinogen-IX 104 3.4.3.1 Intermediates 105 3.5 The iron, magnesium, and cobalt branches 106 3.5.1 The iron branch 106 3.5.1.1 Formation of protoheme 106 3.5.1.2 The hemoproteins 106 3.5.2 The magnesium branch 107 3.5.2.1 Chelation of magnesium 109 3.5.2.2 Esterification of magnesium protoporphyrin-IX 109 3.5.2.3 Reduction of the vinyl group at position-4 109 3.5.2.4 Oxidative formation of the carbocyclic ring 110 3.5.2.5 Reduction of ring D 111 3.5.2.6 Formation of chlorophyll-a 111 X