Advanced Bioinorganic and Medicinal Inorganic chemistry

Lecture 2: Biomineralisation
Biomineralisation is the synthesis of minerals from simple compounds by organisms. This can be for a variety of purposes, including: to lend mechanical strength to bone (calcium phosphates) to orient magnetotactic bacteria (magnetite particlesFe3O4) for storage of iron (ferritin)

Biominerals also include shells, teeth and many different types of skeleton. These compounds can be regarded as the true inorganics in life as they have no organic component c.f. metalloenzymes where most of the molecule is organic. This is not completely true- as will be discussed. One particular area of interest is the molecular control mechanisms that biological systems use to form the well-defined inorganic solid state materials. In fact both inorganic and organic materials are used in exo- and endoskeletons. Sharks and invertebrates use chitin (polysaccharide) structures that are largely organic. In their bones, vertebrates use biomineral constructions that are composite organic/ inorganic consisting of calcium hydroxyapatite and an organic matrix. Why is this the case? the inorganic component brings hardness and pressure resistance without which larger land living animals could not exist the organic matrix consists of collagen, glycoproteins and polysaccharides to give elasticity and tensile strength. Much of modern materials science is concerned with hybrid materials leading to some overlap in the techniques used in these investigations.

Chemical composition Calcium carbonate CaCO3

Mineral form Calcite Aragonite Vaterite Amorphous hydroxyapaptite Whewellite weddelite Gypsum Celestite baryte amorphous

Function/ examples Exoskeletons in corals, egg shells, mollusc shells Gravity sensor Endoskeletons (human and other vertebrates bones and teeth Calcium storage and defense of plants Gravity sensors or exoskeletons Valves of diatoms and defence mechanisms in plants Magnetic sensors Teeth of chitons Iron storage

Calcium phosphates Ca10(OH)2(PO4)6 Calcium oxalate CaC2O4.nH2O Metal sulfates CaSO4.2H2O SrSO4 BaSO4 Amorphous silica SiO2.nH2O Iron oxides Fe3O4 ,-Fe(O)OH.5Fe2O3. 9H2O

Magnetite Goethite, lepidocrocite, ferrihydrite

One property of biominerals must be low solubility under physiological conditions. Formation can take place intracellularly, at the cell surface or in the extracellular space. Important biomineral functions: use as part of mechanically robust instrument and weapons e.g. teeth sensor components e.g. magnetotactic bacteria passive mechanical protection of animal e.g. shells or spikes Both hardness and morphology contribute to these functions. Organic components can have a template function, leading to formation of different phases from the unrestrained system via catalysis and nucleation control.

Biominerals have to be formed and dissolved on much shorter timescales than geological minerals. Calcium carbonate deposition is general controlled by an equilibrium shift due to the consumption of CO2 but there are many processes with greater control for the formation of other biominerals.

Ca2+ + 2HCO3-

CaCO3 (s) + CO2 (g) + H2O photosynthesis

Nucleation and crystal growth:

careful control of these processes can be achieved via highly regulated active transport mechanisms and via specific modulation of surface reactivity.

Often biominerals do not coincide with the regularly encountered forms of the inorganic mineral. This can be achieved by spatial limitations or by other chemicals in the growth medium. EXAMPLES Calcium phosphate Vertebrate bones: 30% 55% 15% elastic fibrous proteins (mainly collagen) inorganic components embedded in glycoproteins (hydroxyapatite) calcium carbonate, silica, magnesium carbonate, citrate, other metal ions.

Bone can be studied with 31P NMR to determine mineral forms. Phosphoproteins are arranged at regular intervals on the collagen fibres and the spacing is correct to allow calcium binding at distances corresponding to the crystalline inorganic phase. Non-biological uses of bones: fertilisers (apatite/ inorganic material. Collagen glue (organic component)

Continuous formation of bone occurs in a peripheral zone with an outer and inner layer of connective tissue containing osteoblast cells. These cells are gradually incorporated into the hardening structure and turn into bone cells. There is continuous exchange of the calcium in bones. This can lead to substitution by other metal ions, which may be present by poisoning, altering the mechanical properties of the bone.

Calcium carbonate The CaCO3 crystals formed in egg and mollusc shells grow in a matrix of proteins and polysaccharides. Significant amounts of carbonic anhydrase are present to produce the required HCO3-. Marine organisms such as corals or molluscs form the mineral in large amounts due to photosynthetic activity which assimilates CO2, increasing the pH of the surrounding medium and shifting the equilibrium towards precipitation.

Amorphous silica It is mainly utilised in unicellular organisms, sponges and several plants. In some plants it occurs in the cell membranes as a passive deterrent. The brittle tips of the stinging hairs of some nettle plants are made of amorpous silica.

Strontium and Barium sulfates Acantharia is a unicellular plankton which features an exoskeleton with a symmetry determined by the inherent crystal structure of the SrSO4 that forms it. The exoskeleton consists of exactly twenty single crystals which can assume complex shapes, and nearly perfect D4h symmetry in some cases.

EXAMPLE: Ferritin When iron is released into the cell from transport proteins it must either be incorporated into a functional role or stored. Ferritin serves as an iron storage site in some animals and plants, with about 13% of the iron in the human body present in this form. Apoferritin is the iron-free form of the protein and has been structurally characterised. It is highly symmetric and roughly spherical within an inner diameter of 80 and an outer diameter of 120 . The inside of the protein is lined with hydrophilic residues as are the three fold symmetric channels- suggesting a route of entry for the metal. It can accommodate up to 4,500 iron atoms with a typical filling of approx. 1,200.

Ferritin has been studied with a number of spectroscopic techniques including EXAFS, Mossbauer and optical spectroscopy. It consists of octahedrally coordinated Fe(III) ions joined by bridging oxide and/or hydroxide ions. The most consistent structure with the spatial parameters is a close packed array of oxygen atoms with iron atoms partially occupying the octahedral holes. There is insufficient data to define the structure unequivocally.