Mammalian Biomolecules metal ion complexes

1. Mammalian Biomoleculesmetal ion complexes • amino acids • histidine, cysteine • nucleotides • purines, pyrimidines • proteins • metalloenzymes, transport proteins • metabolic intermediates • citrate, malate • vitamins • pteridines, riboflavin, thiamin • cobalamine, pyridoxamine • hormones • histamine, adrenaline, DOPA • porphyrins • hemoglobin, cytochromes • polyamines • spermidine, catecholamines

2. metabolic intermediatescitric acid citrate typically functions as a tridentate ligand with the hydroxyl group and two carboxyl groups providing oxygen donor atoms

3. metabolic intermediatescitric acid However, more involved bridged complexes can also form with certain metal ions Mo(V) forms a 2:2 bridged complex Al(III) forms a 3:3 bridged complex where each Al has a different set of ligands

4. metabolic intermediatesmalate malate has three functional groups, however it is difficult for a single metal ion to coordinate to all three

5. Vitamins many vitamins contain multiple functional groups that are capable of coordinating metal ions Vitamin B6 (pyridoxine) Vitamin B1 (thiamin)

6. Hormones Histamine is a hormone that triggers an inflammatory response and also functions as a neurotransmitter Noradrenaline and epinephrine stimulate metabolism dopamine is part of a group of neurotransmitters

7. Plant and Microbial Biomolecules Plants and microorganisms possess a number of unique biomolecules that can coordinate metal ions There are also many metal ion chelators that function to acquire iron from the environment • metal ion chelators • catechol siderophores • hydroxamate siderophores • plant metabolites • chlorophyll • microbial antibiotics • itoic acid, kojic acid, penicillin, tetracyclines

8. Metal ion chelators Iron is an absolutely essential element for all know life forms While we can easily replenish our iron reserves from dietary sources, microorganims must take extreme measures to obtain iron from their environment These macrocyclic compounds form very high affinity metal ion complexes

9. siderophores catechol siderophores enterobactin agrobactin hydroxamate siderophores ferrichrome mycobactin desferrioxamine pseudobactin aerobactin rhodotorulic acid mugineic acid

10. catechol siderophores these multiple catechol groups provide a high affinity metal ion binding site that can satisfy all of the geometric and coordination requirements

11. hydroxamate siderophores

12. hydroxamate siderophoresmetal ion chelation There are multiple potential donor atoms that can participate in metal ion coordination in these siderophores Unlike the situation with many less flexible compounds, these chelators can coordinate metal ions through multiple donor atoms

13. hydroxamate siderophoresmetal ion chelation coordination by three hydroxamate groups is sufficient to satisfy the 6-coordinate requirement of an iron, however the geometry will be distorted

14. hydroxamate siderophoresmetal ion chelation A structure of a vanadium complex with enterobactin illustrates the coordination geometry

15. metal ion chelatorsbinding affinities The formation of a hexadentate chelate with a metal ion leads to extraordinarily high binding affinities These chelators are capable of extracting iron from other complexes The iron chelate is then imported into the microorganism and degraded to release the iron

16. Plant metaboliteschlorophyll Chlorophyll is one of the major plant pigments and functions as a solar collector for photosynthesis

17. bacteriochlorophyll Bacteriochlorophyll contains 7 of the chlorophyll molecules oriented at different angles

18. Photosynthetic dyes Other plant and bacterial dyes can interact with light at different wavelengths Longer wavelength light can penetrate to greater ocean depths, so sea dwelling photosynthetic bacteria use a blue-sensitive dye for solar collection

19. microbial chelators Each of these compounds, unique to microbial metabolism, will form multidentate chelates with metal ions

20. Synthetic chelators A number of synthetic ligands have been designed that contain multiple functional groups to interact with metal ions Used in detergents as a water softener and as a food antioxidant Distortion of the octahedral geometry provides an additional coordination site for a water Since lanthanides form hybrid f orbitals they can use an expanded coordination shell

21. Metal-chelator complexes Even more flexible synthetic chelators have been designed that provide a greater number of donor atoms and bind metal ions with an even higher affinity Here the Mn(II) ion is interacting with 8 different donor atoms from EGTA

22. Metal-chelator complexes Specialized synthetic chelators have been designed that are selective for different metal ions These chelators bind Al(III) in a nearly perfect octahedral coordination geometry

23. Summary • Many lower molecular weight biomolecules are capable of forming strong, multidentate metal ion complexes • These include metabolites, vitamins, and hormones • Plants and microorganisms synthesize specific metal ion chelators that bind to essential metals with extremely high affinities • Synthetic chelators have been designed that minic these natural chelators