Macrocyclic Ligands: Functional Host Guest Systems.

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Macrocyclic Ligands Functional Host Guest
Systems.

• Post Graduate Lecture Course
• January 2000
• Lecture 1

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1. Introduction

• Definitions
• What is a macrocycle?
• A macrocycle is a large ring molecule, normally
  having 12 or more atoms in the ring and normally
  containing heteroatoms capable of binding
  substrates
• Small Rings (3-6), Mesocycles (7-11), Macrocycles
  (?12)

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• Macrocyclic Ligands
• Usually stretch the definition to include
• Ring sizes ? 9
• At least 3 donor atoms

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• Why Macrocycles?
• Biological Systems for
• Photosynthesis
• Oxygen transport
• Redox reactions
• Ion transport

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2. Natural Macrocycles

• 2.1 Cyclic Antibiotics
• 2 types Neutral Macrocycles
• Acyclic Monobasic Acids

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• Enniatin B
• 18-membered ring
• Depsipeptide alternating ?-amino acid and
  ?- hydroxy acid residues
• Valinomycin
• 36-membered ring
• Also Depsipeptide

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• Nonactin
• 32-membered ring
• Macrotetrolide - Alternating ester and ether
  groups
• All complex K selectively vs other alkali metal
  ions.
• Consider some of their X-ray structures.

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Biological Action

• Transport of ions through biological membranes
  (e.g. cell walls)
• Construction Lipids/proteins
• Thickness ca 70Å
• Function selective transport
• Substances capable of transporting ions across
  such membranes are IONOPHORES

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Porphyrins and Related Systems

• By far the most common biological macrocycles
• three main ring types
• Porphyrin Chlorin Corrin

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Vitamin B12 Coenzyme
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Vitamin B12 Coenzyme

• Naturally Occurring Organometallic!
• Cobalt(III) with R-.
• Reduction to Co(II) and Co(I) ?
• R

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Chlorophyll

• Initiates Photo-synthesis
• Absorbs in red
• Oxidation of H2O to O2
• Glucose formation from CO2 and H2O

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Haem Proteins

• Two functions
• - O2 transport and storage
• - Electron Transfer
• Contain Fe porphyrin complexes
• Examples
• - Haemoglobin
• - Myoglobin
• - Cytochrome P450

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3. Synthetic Macrocycles

• 3.1 History
• Baeyer, 1886 - First Reported Macrocycle
• Chem. Ber. 1886, 19, 2184

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• Metal Phthalocyanines, first reported 1928
• The only well known synthetic macrocycle pre-1960

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Other Pre-1960 Macrocycles

• Cyclam (Cyclic Amine) Alphen, Recl. Trav. Chim,
  1937, 56, 343.
• Dibenzoaza-crowns Krässig and Greber, Makromol.
  Chem., 1953, 11, 231.

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3.2 Nomenclature

• 1,4,7-trithiacyclononane trithia-9-crown-3
  9aneS3
• 1,4,8,11-tetraazacyclotetradecane tetraaza-14-
  crown-4 14aneN4.
• 4,13-diaza-1,7,10,16-oxacyclooctadecane
  diaza-18-crown-6 18aneN2O4.

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3.4 Synthesis General Methodology

• Formation of One Bond
• Linear compound with a reactive group on each
  end.

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Examples

• This head to tail method is sometimes known as
  the snake reaction!

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• Formation of two Bonds
• 1 1 Cyclisation
• Most Commonly Used Method of Macrocycle
  Preparation

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• Examples