Topic 2: Inorganic Chemistry II - Transition Metal Ions in Biological Systems

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Essential Elements for Life

Include carbon, hydrogen, oxygen, nitrogen, minerals, and electrolytes like sodium, potassium, and calcium

Transition Metal Ions

• Constitute about 0.1% of the atoms in the human body as trace elements

• Nine essential transition metals are V, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Mo

Metalloproteins

Form when transition metal ions are natural constituents of proteins

Why are Transition Metal Ions Used in Biology?

They readily change oxidation states, allowing them to pick up and release electrons useful for redox chemistry

Three essential roles of metalloproteins

1. Transport and Storage

2. Enzymes (metalloenzymes)

3. Redox Reagents

Proteins

Polymers made of amino acids linked by peptide (amide) bonds

Protein structures

secondary (alpha helix, beta sheet), tertiary (folded shape), quaternary (dimers/tetramers)

Specific shape of a protein

designed to catalyze one specific reaction

Movement and storage of oxygen

accomplished by iron-containing proteins hemoglobin (in blood) and myoglobin (in muscles)

Iron transport protein

transferrin

Haem group

iron-porphyrin complex acting as tetradentate, square planar ligand that chelates the iron

Hemoglobin structure

tetramer containing four haem groups, making O₂ about 70 times more soluble in blood

Deoxy-haemoglobin

contains Fe²⁺ (d⁶ High Spin), paramagnetic

Oxy-haemoglobin

iron center changes to diamagnetic upon O₂ binding, best understood as low spin Fe³⁺ (d⁵) antiferromagnetically coupled to superoxide (O₂⁻)

Carbon monoxide toxicity

CO binds more strongly to hemoglobin than O₂, displacing oxygen

CO₂ interacts with protein periphery to promote O₂ release in tissues

Cytochromes

iron-containing proteins with haem groups that facilitate electron transfer by cycling iron between Fe(II) and Fe(III)

Photosystem II

converts H₂O → O₂ + 4H⁺ + 4e⁻

contains multiple Mn atoms and one Ca atom

Manganese centers

cycle through oxidation numbers Mn(II), Mn(III), Mn(IV) to deliver four electrons

Superoxide dismutase (SOD)

enzyme that destroys reactive superoxide ion (O₂⁻)

SOD reaction

converts O₂⁻ to O₂ and peroxide (O₂²⁻ → H₂O₂)

SOD metals

uses Cu and Zn

Role of Zn in SOD

structural, holds complex in place

Role of Cu in SOD

electron shuttle cycling between Cu²⁺ and Cu⁺

Step 1 of SOD reaction

Cu²⁺–SOD + O₂⁻ → Cu⁺–SOD + O₂

Step 2 of SOD reaction

Cu⁺–SOD + O₂⁻ → Cu²⁺–SOD + O₂²⁻ (as H₂O₂)

Role of protein superstructure

protects complex and determines molecule access to metal center

Ligand fine tuning

ligands adjust the metal center to catalyze one specific reaction efficiently under mild biological conditions

Cisplatin

cancer drug cis-[PtCl₂(NH₃)₂], square planar geometry, only cis isomer is active

Cisplatin discovery

1965, Barnett Rosenberg, Michigan State University

platinum compounds prevented bacterial cell division

FDA approved 1978

Cisplatin mechanism

hydrolysis forms [Pt(NH₃)₂(OH₂)Cl]⁺, which coordinates to DNA via N7 of guanine/adenine

Cisplatin-DNA adduct

kinks DNA helix, blocks DNA repair, causes cell death

Technetium (Tc)

no stable isotopes, all radioactive

Technetium-99m

metastable isomer used in medical imaging (e.g., heart blood flow)

Technetium coordination chemistry

Tc ions combined with ligands to form injectable complexes for targeted imaging

Chelation therapy

treats toxic metal buildup using chelating agents to form excretable complexes

Chelating agent mechanism

binds selectively with toxic metals to form complexes removable by kidneys

Chelating ligands

usually polydentate with high formation constants (β), stabilized by chelate effect

Ligand selection

guided by hard/soft acid-base principles

Chelation challenges

chelates may remove essential metals, requiring supplements

EDTA⁴⁻

common but non-selective chelating agent

DMSA (meso-2,3-dimercaptosuccinic acid)

removes soft metals like Hg²⁺ and Pb²⁺ using sulfur donors

Deferasirox

reduces acute iron levels (e.g., thalassemia)

Fe³⁺ prefers hard donors (O, N) present in deferasirox

Oxidation state calculation

metal charge = complex charge − sum of ligand charges (e.g., [Re(CO)₅Cl] → Re⁺¹)

IUPAC definition of transition element

element with an incomplete d subshell or forming cations with incomplete d subshells

Zinc exclusion

Zn not a transition element because Zn and Zn²⁺ have full d¹⁰ configurations

d-electron count

formula = (Group number − Oxidation state)

Coordination sphere

octahedral (6-coordinate) or square planar (4-coordinate)

Bidentate ligands

form two bonds to metal (e.g., ethylenediamine, oxalate)

iodide is not bidentate

Octahedral crystal field splitting

d orbitals split into t₂g (dxy, dxz, dyz) and eg (dx²−y², dz²)

High Spin (HS) vs Low Spin (LS)

determined by Δ₀ vs pairing energy (P)

If Δ₀ < P

complex is high spin

If Δ₀ > P

complex is low spin

Electron counts capable of HS/LS

d⁴, d⁵, d⁶, d⁷

Spectrochemical series

order of ligand field strength: halides < oxygen donors < nitrogen donors < carbon donors

Magnetism

diamagnetic if all paired, paramagnetic if unpaired electrons present

Magnetic moment formula

μ = √(n(n+2)) μ_B

Jahn-Teller distortion

occurs in d⁹ configurations (e.g., Cu²⁺) due to partial filling of e_g orbitals

Cause of Jahn-Teller distortion

degenerate e_g orbitals split into two energy levels when distorted

Result of Jahn-Teller distortion

energetically favorable stabilization by lowering energy of partially filled orbital