1IntroductionThe relative abundance of the elements, the way that they speciate andthe properties of the resultant molecules have largely determined the courseof biological evolution. It is clear, however, that unlike the chemical speciationsthat occur in the inorganic environment those that occur in biological systemsare carefully controlled to facilitate some process. Living organisms survivebecause they direct the type and reactivity of the elements and moleculeswith which they associate.In order to appreciate this, imagine a mineral EL1that haspartly dissolved in an aqueous solution to release the element (E) and itsassociated ligand (L1). In this solution is a second ligand L2that is also capable of associating with element E. At equilibrium the systemwould exist as shown inFig. 1. Thefree dissociated ion of element E in the environment is shown as Ee.Possible interactionsof an element (E) with a variety of ligands (L1–L7). The element enters the aqueous environment by dissolution of the mineral(EL1) and dissociates to form a free metal ion (Ee)capable of speciating with other dissolved ligands (EL2). In thepresence of living organisms there may be other ligands released into thesystem (L3) that could form biofilms on the mineral, binding theelement (EL3) and potentially removing E from the system by sedimentation.A cell might also produce a membrane bound ligand (L5) capableof sensing the element E which may also enter the cell through a ion pump(L6) to be released in the cytoplasm (Ei) where it canspeciate onto intracellular ligands (L4). Alternatively anion transportingchannels (L7) may allow speciated forms of the element (EL1)direct access into the cell.Consider what would happen now if an organism that could act as a sourceof additional ligands (e.g., L3) resided within this system.Such ligands might be humic acids or bacterial exopolymers and they wouldraise at least two additional possibilities. First, the biological productsmight coat the surface of the mineral forming biofilms that interacted withelement E resulting in it becoming speciated onto this surface (EL3).Second, if this particle sedimented out of the aqueous environment there wouldalso be a loss of the surface-bound elements from the system. The systemwould now have progressed from an equilibrium situation to a kinetically drivenstate that determined the residence time of the element (E) in the aqueousphase.This example of the speciation of an element onto a surface and the sedimentationof such an organically coated particle has been used to explain both the compositionof the marine environment1and the occurrenceof geochemical cycling.2It is a powerful argumentthat when carried to its conclusion provides an explanation for the compositionof the extracellular fluids of many organisms since these are thought to reflectthe concentrations resulting from such biogeochemical processes.Let us, therefore, try to complete this model by considering the otherspeciation effects that a living cell could have on this system. Cells controlthe type and reactivity of the elements with which they associate. They dothis by isolating heterogeneous aqueous compartments within hydrophobic cellmembranes. This is achieved by trapping molecules with hydrophilic ligands(L4) and by synthesizing hydrophobic ligands that become trappedin the membrane itself. These form localised element-sensing molecules(L5) or vectorial channels containing elaborate structural ligands(L6,L7). Various elements become speciated with theseligands and thus segregated from the bulk phase to provide the organisationalbasis that defines living organisms.From this brief introduction it will be apparent that the definition ofspeciation as ‘the occurrence of an element in separate identifiableforms’ effectively requests a review of the whole of inorganic biochemistryand its relationship to biogeochemical cycling. This is an almost impossibleremit and in order to introduce some shape into this overview we pose threequestions.(1) Are the laws of inorganic chemistrydirectlyapplicable tobiological systems? If the operational answer to this question is ‘Yes’then we have a common starting ground for chemists and biologists. If theanswer is ‘No’ then we have to identify how living systems aremodified by factors such as nanoscale dimensions or localised energy inputs.(2) How diverse are the speciation processes that occur in biological systems?This, in effect, questions how many ‘identifiable ligands’ orspeciation pathways have to be considered either in the external environmentor within the cell. In order to control the types of speciation that haveto be discussed we have chosen to base our analysis on a few examples fromthe different aqueous, mineral and lipid environments that are involved inliving systems.(3) Does this provide a rational context for considering the toxicity ofsome speciation pathways that might otherwise appear to be disparate phenomena?