Studies on the synthesis and reactivity of copper thiolate and thioamide complexes : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University

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February 1984

STUDIES ON THE SYNTHESIS AND REACTIVITY OF COPPER THIOLATE AND THIOAMIDE COMPLEXES

A thesis presented in partial fulfilment of the requirements for the Degree of Doctor of Philosophy

at Massey University

by

Alistair Gavin Cameron Bin gham

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ACKNOWLEDGEMENTS

I would like to thank sincerely my supervisors Dr E . W . Ain scough and Dr A . M . Brodie for their direction, assistance and encouragement in all a spects of the research programme .

The contribution of the following is also gratefully acknowledged:

Drs K . L . Brown and G . A . Gain s f ord, Chemistry Division, D.S . I . R . , Petone for the crystal structure analys es of the compounds [ Cu(3-Mep y ) 3Cl]

and [ Cu(tztdz}Br] respectively .

Drs E . N . Baker and B . F . Anderson, Mas sey University, for crystal structure data of [ Cu(4-Mep y ) 4 cl2 J . H2o,

Profes sor R . Hodges, Ma ssey University, and Dr G . J . Shaw, Applied

Biochemistry Division, D . S . I . R . , Palmerston North, for ma s s spectra and help ful discussions . Professor T . M . Loehr and Dr J . E . Plowman, Oregon Graduate Centre, Beaverton, Oregon for recording resonance Raman spectra . Dr G . E . Norris for the provision of azurin .

Profes sor A . D . Campbell, Otago University, for microanalyses .

Mrs Glen da Shaw for typing this thes is .

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ABSTRACT

In response to a clear need for a more s ys t ematic approach to the study of the in teraction o f copper with ligands containing the

sulphhydryl group, or in thioamide tautomeric equilibrium with such, cuprous, cupric and mixed valence complexes o f ligands con taining a thiolat e or thioamide moiet y have been synthesised and characterised by spec t roscopic, mag netic and crys tallographic t echniques. In certain cases t heir reactivit y in aliphatic and aromatic nitro gen base solven t s and nitromethane have been investigated.

Full names for the ligand abbreviations appear at the end of the abstract and ligand s tructures ma y be found in Figures a t the beginning of the appropria te chap t er.

The visible, esr and resonance Raman spectra o f t he t yp e I, copper pro tein, azurin from Alcaligenes denitrificans, have been recorded and comp ared with other t ype I pro tein s . Through comparison with the

spec t ral fea t ures o f a series o f clus ter complexes

(where Y ^� C H3CN or H2o, and X ^� BPh4,

II I

[ Cu 6cu 8(mea ) 1

5

l) Cl 5 . 7H2o, the so-called

•unusual• spectro scopic features o f the t yp e I pro t ein s have been

re-in terpreted a s being normal phenomena o f a Cu(II ) -thiola te interaction coupled with specific geometrical requiremen t s .

Inves tigation o f the mbtH ligand s ys t em has led to the reformula tion of a number of incorrec tly formula ted copper complexes as [ Cu(mbtH ) 2Cl) or [ Cu(mbt ) ) following succes s f ul removal o f a disulphide con taminan t.

In support of such, similar cuprous compounds o f genera l formula

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[ Cu(LH ) 2X] (LH = etmbtH, X ⁼ Cl, Br, I; LH = mbtH, X = Br, I;

LH ⁼ mmi mH, X = Cl ) , [ Cu(LH ) X] . xH20 (LH = mbimH, mpyH, p hmtzH, Ph2PS2H, X = Cl, Br; LH = mmimH; X = Br ) and [ Cu(L ) ] (L bimet, dimtdz, dipmim etmbt, mp y, phmtz ) have been p repared f ro m s imila r ligand s y s t ems . The intera c t ion o f a number o f t hese complexes with pyr idine led t o o xida t ion of o rgano-sulphur to sulp hate with the p roduct ion of [ Cu(p y ) 4so4 ] . 2H2o . Thi s reaction i s postula t ed to occur via two oxidis ing spec i es

[ Cu(p y ) OH ) ] o r [ Cu(p y ) 0] depending on whether halides a re p resen t o r 2 2 ^X absent i n the react ion solut ions . Simila r sulphato spec ies a re seen when quinoline and 3-ethylp yridine a re used a s solven t s . However, compounds of general fo rmula [ Cu(LH ) 2X] and [ Cu(LH ) X] yield the complexes

[ Cu(3-Mep y ) 3Cl] and [ C u(4 -Mep y ) 4cl2] . H2o, f ro m the solven t s 3-methyl- pyridine and 4 -methylp yr i dine respectively, whi ch have been s t ructurally characterised by X-ra y c rystallog raphy .

The cup r i c and mi xed valence complexes [ Cu(t tzH ) 3X2] (X = Cl, B r ) , [ C u( t tzH ) 2Br 2] , [ CuiiCui 3 ( t tz ) 5] , [ Cu IICu I (mmi m ) (mmi mH ) 2c12] ,

[ Cu IICu I ( mmimH ) 2 C 13] , [ Cu ( mbi m ) 2 ( H2 0 ) ( NH3 ) ] , [ Cu ( mbi m ) 2 ( H2 0 ) ] ,

[ C u(d ipmi m ) Cl] and [ Cu(et u ) OH] have been p repared and cha racter i sed by vi s i ble, inf ra red, and es r spec t roscop y .

When [ Cu(t tzH ) 3sr2] i s ref luxed i n n i tromet hane, a new cup rous complex [ Cu(tztdz ) Br] i s p roduced i n which mod i f icat ion o f the t tzH

ligand to p roduce the new o rgan i c mo iety tztdz has occur red, con f i rmed by X-ray c rystallo g raphy . Simila rly the compounds [ Cu(tztdz ) Cl] ,

[ C u(tztdz ) Cl2] and [ Cu(mimmimz ) Cl2] are postula ted f rom the in teraction of [ Cu(t tzH ) 3cl2) and [ Cu11cu1(mmimH ) 2cl3) with n i t romethan e .

Wi th reference to well-def ined litera ture examples the techn i que o f

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esr spectro scopy is shown to discriminate between equatorial dono r atom

posit ion o f fundamental parameters. The n ew compounds s ynthes i sed:

[ Cu11cu12(di metH2 ) (dimetH ) 3Cl] , [Cu11cu13(dimetH2 ) 3(dimetH ) (C l04 ) 4 ], [ Cu11cu13(dimtolH ) 5 ], [ Cu11cu1 3(dimprolH ) 5] , [ C u(mpoH2 ) (mpoH ) (Cl04 ) ], [ C u(phenylglyoxaldt sc ) ] , [ Cu(benzild t s c ) ] . H2o and

[ Cu(3-n-heptoxy-2-oxobut yraldehydedtsc ) ] have been a s s i gned dono r set s o n the bas i s o f thei r respec t ive esr s ignals. Simila rly this has been don e for a number o f unisola t ible species p roduced i n s i tu f rom interac-

tion of various cupric salt s with a number of sulphhydryl and t hioamide cont aining ligands.

bimetH dimtdzH dipmimH dimetH dimp ro

f

^H

dimtolH22 dt sc etmbtH e�H mbimH mbtH meaH mimmimz mmimH mpoH2 mp yH phmtzH Ph2PS2H p y ttzH tztdz

Ligand abbreviat ions

2-benzi midazoleethanethiol

2 , 5 -dimercap t o -1 , 3 , 4 -thiadiazole 4 , 5 -diphenyl-2-mercap t o i midazole 1 , 2-dimercaptoethane

2 , 3-dimercap topropanol 3 , 4 -dimercap totoluene dithiosemicarbazide

6-etho xy-2-mercaptobenzo thiazole 2-mercaptothiazoline

2-mercap tobenzimidazole 2-mercap tobenzo thiazole cysteamine

3-(2 , 1-methylimidazolyl ) -2 , 1-methylimidazoline thione

2-mercapto-1-methylimidazole 2-mercapto-3-pyridinol

2-mercap topyridine

2-mercapto-4 -phen ylthiazole diphenylpho sphinodithioic acid p yridine

2-mercap to thi azoline

3-(4 , 5 -dihyd ro-2-thiazolyl ) -2-thiazolidinethione

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Contents

GENERAL INTRODUCTION

Chapter 1

Pa rt 1

1 . 1 1.1 . 1 1 . 1 . 2 1 . 2

l. 2.1 l . 2. 2 l . 2 . 3

Part 2

1.3 1 . 4

l . 4 . 1 l. 4 . 2 l . 4 . 3 1 . 4 . 4 1 . 5

Fundamental esr theory

SPECTROSCOPIC STUDIES OF AZURIN FROM ALCALIGENES DENITRIFICANS AND SMALL MOLECULE ANALOGUES OF ITS COPPER SITE Azurin

Introduction Experimental Source of azurin In strumentation

Results and discus sion

Electronic absorption spectroscop y Resonance Raman spectroscop y

Electron spin resonance spectros cop y Summa ry

Small molecule models for the type I copper protein s

Introduction

Synthesis of the compounds Results and discussion In f rared spectra

Electronic spectra Es r spectra

Resonance raman spectra

Structure of the model complexes

page 1 4 7

7 7 11 11 11 11 11 15 21 24 25

25 29 31 31 31 34 38 38

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1.6

1.7 1. 7. 1 1. 7. 2

Chapter 2

2.1 2.2 2.3 2.3.1 2.3.2 2.4 2.5 2.5.1 2.5.2

Chapter 3

3.1 3 .1.1 3 .1. 2 3 .1. 3 3 .1. 4 3 .1. 5

An interp retation o f the structural requirements neces sary f o r the p roduction of the distinct

spectra l f eatures o f the type I blue copper p roteins Summa ry

Experimenta l Ins trumentation

Preparation o f the comp lexes Ref erences

THIOLATE AND THIOAMIDE COMPLEXES OF COPPER(I ) Introduction

Synthesis of the compounds Inf ra red spectral analysis

Structura l aspects of the p repa red compounds Cup rous thioamide compounds

Cup rous thio late compounds

Trends in the fo rmation of complexes Experimental

In strumentation

Preparation o f the comp l exes References

REACTIVITY STUDIES OF CUPROUS THIOAMIDE AND THIOLATE COMPLEXES IN ORGANIC BASES

Introduction

Results and discus s ion Reactions in neat pyridine

Reactions in neat quino line and 3-ethylp yridine Reactions in neat 3-methylp yridine

Reactions in neat 2-chlo ro and 3-chloropyridine Reactions in neat 4-methy lpy ridine

42

47 49 49 50 51 56 56 5 9 66 73 73 76 77 81 81 81 85 88

88 89 89 97 97 102 103

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3 .1. 6 3 .1. 7

3.2 3. 2. 1 3.2.2

Chapter 4

4.1 4 .1.1 4 .1. 2 4 .1. 3 4 ^.1^.4

4.2

4.3

4.4 4.4.1 4.4.2

Chapter 5

5. 1 5.2

Reactions in neat 1, 2-diaminoethane Reactions of other trans ition meta l ions Conc lusion

Summary Experimenta l Instrumentation

Preparation o f the comp l exes References

FURTHER ASPECTS OF THE OXIDATION OF THIOLATES IN THE PRESENCE OF COPPER

Introduction

Results and di scus s ion

Substrates capable o f being oxidised

Identif ication o f the proposed reactive spec ies Characteri sation o f the reactive spec i es

Ox idation o f compounds o f the type CuL3x - a s ynthetic route for production o f [ Cu{p y ) O]

X

Ox idation o f the sulphhydryl group in so lvents other than p yridine

Bacteria l oxidation o f sulphur Summary

Experimenta l In strumentation

Synthes is of the comp l exes References

CUPRIC COMPLEXES FROM THIOAMIDE LIGANDS Introduction

Synthes i s of the compounds Results and d i scus s ion

106 107 109 110 112 112 112 116 118

118 122 122 125 126 133

138

140 141 142 142 142 14 7 1 4 9 1 4 9 152 152

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5 . 2 .1 5 . 2.2 5.2 . 3

5 . 3 5 . 4 5 . 4.1 5 . 4.2

Chap t e r 6

6 . 1 6.2 6. 2. 1 6.2.2 6.2.3 6.2 . 4 6.2 .5 6 . 2.6 6.2.7 6 . 3

6.4 6.4 . 1 6.4.2

Comp lexes of 2 -mercap tothiazol ine

Comp lexes of 2 -me rcapto-1-met hy l imidazol e

Comp lexes o f 2 -mercap tobenzimidazole, 4, 5 -dipheny l- 2 -mercap toimidazole and 2 -me rcaptoimidazol ine

React ivit y s tudies in ni t romethane Expe r iment a l

Ins t rumentat ion

Preparat ion of the comp lexes Ref e rences

A SPECTROSCOPIC INVESTIGATION OF SOME CUPRIC AND MIXED VALENCE THIOLATE C OMPLEXES

Int roduction

Synthe s i s of the compounds

Cha racterisation of the comp lexes

Cup ric comp lexes with p roposed s4 donor s ites Cup ric comp lexes with p ropos ed S202 donor sites Cup ric comp lexes with p roposed S2N2 donor s i tes Cup ric comp lexes with p roposed so3 donor s i tes Cup r i c comp l exes wi th p roposed 04 donor sites Graphic p lots of g l l versus

I

^{A l l}

I

Elect ronic spec t ra

Use of the es r technique in p robing dime ric cup r i c interact ions

Exper imenta l Ins t rumentation

Prepara t ion of the comp lexes

153 166 172

176 18 5 18 5 18 5 18 9 19 1

191 193 19 8 19 8 205 207 210 2 11 2 13 2 13 2 16

2 2 3 2 2 3 2 2 3

References 2 2 8

A summa r y of the pos s ible factors leading t o s tabi l - 2 32 isation of cup r i c thiolate or thioamide comp lexes

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1.1 1.2

1.3

1.4

1.5 1.6 1.7 1.8 2.1

2.2 2.3

2.4

2.5 2.6 2.7

3 . 1

L i s t o f Tables

Spec t ro scopic and redox p roperties o f var ious azu

�

in s Elect ronic band maxima fo r Ale. denitrif icans and Ps. aeruginosa azurins and Populus n igra

pla s tocyanin

Resonance Raman f requencies, rela tive inten s ities and

possible ass ignmen t s of the p roteins between 260 and 500 cm -1

Resonance Raman combination and overtone f requencies o f azurin f rom Ale. den i t r if icans

Es r pa rameters for azurin t ypes

The bes t models to dat e for t ype I blue p rotein s Elect ronic spec t ra for small molecule analogues Es r parameters for the complexes

Propo sed fo rmulations o f the Cu-2-mercap tobenzo thiazole system

Analytical data for the complexes

Elemen tal analysis f igures f o r va rious Cu(II ) -2-mercap to benzo thiazole p reparations

Inf ra red spectral changes with respect to the f ree ligand on coo rdination of sulphur and nitrogen

Thioamide band pos i t ions

The geomet ry of va rious cup rous thioamide complexes Na ture of the p roduc t fo rmed f rom the in teraction of a thioamide ligand and the respective cup ric salt

Analyt ical figures for the compounds p roduced f rom reactivit y s tudies

Page 8 14

17

19

23 27 32 35 58

61 65

69

71 75 79

91

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3 . 2

3.3 3.4 4.1

4.2

5.1 5.2 5 . 3 5.4 5.5

6.1 6 . 2

In f ra red and Raman active bands for various s ymmetries of so42- radicle

Sulphate complexes and p rincipal inf ra red bands Bond lengths and angles for [ Cu{3-Mepy ) 3Cl]

Es r pa rameters for reaction solution s where Cl and B r were absent

Es r pa rameters f or reaction solutions containing Cl and Br

Elemental analyses and magnetic data for the complexes Selected p rincipal inf ra red vibrations for the complexes Electronic spectra for the complexes

Electron spin resonance parameters f or the complexes Bond lengths and angles for [ Cu{tztdz ) Br]

Elemental analysis and magnetic data for the complexes Electronic and es r spectral data for the complexes

9 4

96 99 127

128

1 5 5 156 157 158 179 197 200

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Lis t of Figu res

1 . 1 Dimen sions o f the copper site in azu rin and pla s tocyanin 1 . 2 Elect ronic absorption spect rum o f Ale . denitrificans

azu rin

1 . 3 Resonance Raman spect rum o f Ale . denit rificans azu rin 1 . 4 Esr spec t rum o f Ale . denit rificans azu rin

1 . 5 Structures o f the bes t type I models

1 . 6 Structu re s and abbreviations o f ligands appea ring in this section

1 . 7

1.8 Resonance Raman spect rum of [ Cu

1 . 9 Ligand g eome t r y f o r the Cu ( II) site in

1.10 Relatio n o f copper geome t r y and the s ize o f the

2 . 1

2 . 2 2 . 3

3 . 1 3.2

3 . 3 3 . 4

3 . 5

IA1 1 1 es r parameter

Thiol-thioketo tau tomerism f o r imidazole and thiazole skeletons

Structure s o f the ligand and their abbreviations Some coo rdinating modes of the mbt ligand

Structure s and nomencla ture for Chapter 3 ligands

St ructure of [ Cu ( 3-Mepy)3Cl)

Diag ram showing in finit e linear Cu-Cl . . . Cu chains in [ Cu(3-Mep y)3Cl]

A s t ereo scopic view of [ Cu ( 3-Mepy)3Cl) chains showing Cl . . . H dis tances le s s that 3�

Page 10 13

16 2 2 2 8 30

37 39 40

48

56

60 78

9 0 9 2

·g8 101

101

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3 . 6 3 . 7 3 . 8

4 . 1 4 . 2 4 . 3

4.4 4 . 5 4.6 4 . 7

5 . 1 5 . 2

5 . 3

5 . 4

5 . 5 5 . 6 5 . 7 5 . 8 5.9 5.10

Esr spec t rum o f [Cu ( en)2( mbt)2 ] . H2o in N , N'-dimethyl f o rmamide

Produ c t s of thiol o xidation ^·

Ligands discussed in this chapter and their abbreviations Reaction o f CuCl dis solved in p yridine with a varie t y o f compounds

Reac tion of cup ric species with some sulp hu r sources Esr spec t ra o f cup ric species in pyridine

'

Ligands encountered in this chapter and their abbreviations Flow diag ram for the p roducts de rived f rom 2-mercap to-

thiazoline

II I

Inf ra re d spect ra o f [Cu Cu 3( ttz)5 ] and [Cu ( ttzH)3cl2]

Elect ronic spec t ra o f [Cu ( t tzH)3cl2] and

E s r spec t ra of [Cu ( t tzH)3Br2 ] II I

and [Cu Cu 3( t tz)5

Flow diag ram f o r complexes o f 2-mercap to-1-methylimidazole E s r spec t ra o f Cu ( II)-4 ( mmimH) and Cu ( II)-4 ( mp yH)

E s r spec t ra o f [Cu ( etu)OH ] and [Cu ( tztdz)Cl2 ] A possible s t ructu re for [Cu ( e tu)OH ]

Ligand geome t r y about copper in [ Cu ( tztdz)Br ]

105 106 108

119 121 123

124 129 135 136

151 154

161

163

165 168 170 174 176 178

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5.11 F la t tened boa t character and non-p lanar rings in 180 [ Cu ( tzt dz)Br]

5.12 A mechanism f o r the f o rmation o f [ Cu ( tztdz)Br] f rom 18 2

5.13 A f low diag ram f o r reactivit y s t udies in nit rome t hane 18 4

6.1 Ligands discussed in this chapter and their abbreviations 19 4 6 . 2 Rep resenta tive e s r spectral lin eshapes for various 199

6.3

6.4

6.5

6.6

6.7

6.8

equatoria l donor a tom s e t s II I

Es r spect ra o f [ Cu Cu 3 ( dimp ro lH)5] and Cu ( II)-2 ( 1,2- dime rcaptoethanedisodium s a l t)

Es r spec t ra o f [ Cu ( mpoH)�poHz)C l 04 ], Cu ( II)-2 ( 2-mercapto-3-pyridinol) and Cu ( II)-2 ( thioma lic acid)

E s r spec t ra o f [ C u ( pheny l g l yoxa ldt sc)] and Cu ( II)-2 ( penicil lamine)

Es r spect ra of Cu ( II)-( dime rcap top ropanesu lphonate) and Cu ( II)-4 ( thiog l yco late)

A p lot o f g11 versus IA11I for va rious donor atom s e t s

Low and high field esr spect rum o f [ Cu ( KTS)]

2 04

2 06

2 09

212

2 14

2 2 0