UNIVERSITY OF SOUTH AFRICA (UNISA)
College of Agriculture and Environmental Sciences — Department of Chemistry
⋄
Platinum Complexes and Their
Interaction with DNA
Assessment 4 — 2026
⋄
Module Code: CHE3701
Module Name: Inorganic and Bioinorganic Chemistry
Assignment No.: Assessment 4
Due Date: [insert due date]
Semester: 2026
Unique Number: [insert unique number]
Submitted in partial fulfilment of the requirements for CHE3701
at the University of South Africa.
,UNISA | CHE3701 Platinum Complexes and DNA Interaction
Contents
1 Question 1: Platinum Complexes 3
1.1 1(a)(i) Chemical Properties of Pt(II) and Pt(IV) . . . . . . . . . . . . . . . . . . . . 3
1.2 1(a)(ii) Biological Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 1(a)(iii) Three Medicinal Platinum Complexes . . . . . . . . . . . . . . . . . . . . 4
1.4 1(b) Structures of Cisplatin and Transplatin . . . . . . . . . . . . . . . . . . . . . 5
1.5 1(c) Structural and Biological Comparison . . . . . . . . . . . . . . . . . . . . . . 5
1.6 1(d) Square-Planar Geometry of Pt(II) . . . . . . . . . . . . . . . . . . . . . . . . . 6
2 Question 2: Cisplatin and DNA 8
2.1 2(a) Interaction of Cisplatin with DNA . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.1 Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.2 Type of bond formed and site of attack . . . . . . . . . . . . . . . . . . . . 8
2.1.3 Types of DNA damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.4 Cellular consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2 2(b) Mechanism of Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3 Question 3: Trans Effect and Synthetic Routes 12
3.1 3(a) Trans Effect and Trans Influence . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.2 3(b) Synthetic Routes to Cisplatin and Transplatin . . . . . . . . . . . . . . . . . 13
3.2.1 Route to cisplatin: from potassium tetrachloroplatinate(II) . . . . . . . . . 13
3.2.2 Route to transplatin: from tetraamineplatinum(II) chloride . . . . . . . . . 13
4 Question 4: Chloroquine and Ferroquine 15
4.1 4(a)(i) Structure of Chloroquine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.2 4(a)(ii) Structure of Ferroquine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Page 1 of 18
,UNISA | CHE3701 Platinum Complexes and DNA Interaction
4.3 4(b) Effect of the Iron-Containing Group . . . . . . . . . . . . . . . . . . . . . . . 16
Reference List 18
Page 2 of 18
, UNISA | CHE3701 Platinum Complexes and DNA Interaction
Question 1: Platinum Complexes
1(a)(i) Chemical Properties of Pt(II) and Pt(IV)
Discuss the chemical properties of platinum(II) and platinum(IV), comparing their elec-
tronic configuration, geometry, stability and reactivity.
Platinum(II) is a d8 metal centre. The eight d electrons occupy the lower-lying dxz , dyz , dz 2 and
dxy orbitals, leaving the high-energy dx2 −y2 orbital empty. Because this orbital points directly
at the four incoming ligands, a square-planar, four-coordinate geometry is strongly favoured,
with dsp2 hybridisation and bond angles of 90◦ . This arrangement leaves the axial positions
above and below the plane open, so square-planar Pt(II) complexes are coordinatively unsatu-
rated and kinetically labile: they undergo associative (SN 2-type) ligand-substitution reactions
readily, proceeding through a five-coordinate trigonal-bipyramidal transition state. This lability
is what allows Pt(II) drugs such as cisplatin to aquate inside the cell and bind covalently to
DNA.
Platinum(IV) is a d6 metal centre and adopts an octahedral, six-coordinate geometry with
d2 sp3 hybridisation. All six d electrons pair up in the three lower-energy t2g orbitals (dxy , dxz ,
dyz ), giving a low-spin, substitutionally inert configuration. Ligand exchange at Pt(IV) is ex-
tremely slow because all six coordination sites are already occupied and no low-energy asso-
ciative pathway is available; the complex must first be reduced to Pt(II) before substitution
can occur readily. This kinetic inertness is pharmacologically useful: Pt(IV) complexes such
as satraplatin are administered as prodrugs that survive the gut and bloodstream intact, and
are reduced intracellularly by ascorbate or glutathione to release the active, ligand-labile Pt(II)
species with loss of the two axial ligands.
In summary, Pt(II) is square planar, kinetically labile and directly cytotoxic, while Pt(IV) is
octahedral, kinetically inert and biologically activated only after in vivo reduction. Pt(IV) com-
plexes are also generally more resistant to oxidation (they are already in a higher, more stable
oxidation state for platinum), whereas Pt(II) is comparatively easily oxidised back to Pt(IV) by
cellular oxidants, a property that is deliberately exploited in prodrug design (Miessler, Fischer
and Tarr, 2014).
Page 3 of 18
College of Agriculture and Environmental Sciences — Department of Chemistry
⋄
Platinum Complexes and Their
Interaction with DNA
Assessment 4 — 2026
⋄
Module Code: CHE3701
Module Name: Inorganic and Bioinorganic Chemistry
Assignment No.: Assessment 4
Due Date: [insert due date]
Semester: 2026
Unique Number: [insert unique number]
Submitted in partial fulfilment of the requirements for CHE3701
at the University of South Africa.
,UNISA | CHE3701 Platinum Complexes and DNA Interaction
Contents
1 Question 1: Platinum Complexes 3
1.1 1(a)(i) Chemical Properties of Pt(II) and Pt(IV) . . . . . . . . . . . . . . . . . . . . 3
1.2 1(a)(ii) Biological Mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 1(a)(iii) Three Medicinal Platinum Complexes . . . . . . . . . . . . . . . . . . . . 4
1.4 1(b) Structures of Cisplatin and Transplatin . . . . . . . . . . . . . . . . . . . . . 5
1.5 1(c) Structural and Biological Comparison . . . . . . . . . . . . . . . . . . . . . . 5
1.6 1(d) Square-Planar Geometry of Pt(II) . . . . . . . . . . . . . . . . . . . . . . . . . 6
2 Question 2: Cisplatin and DNA 8
2.1 2(a) Interaction of Cisplatin with DNA . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.1 Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.2 Type of bond formed and site of attack . . . . . . . . . . . . . . . . . . . . 8
2.1.3 Types of DNA damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
2.1.4 Cellular consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
2.2 2(b) Mechanism of Apoptosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
3 Question 3: Trans Effect and Synthetic Routes 12
3.1 3(a) Trans Effect and Trans Influence . . . . . . . . . . . . . . . . . . . . . . . . . 12
3.2 3(b) Synthetic Routes to Cisplatin and Transplatin . . . . . . . . . . . . . . . . . 13
3.2.1 Route to cisplatin: from potassium tetrachloroplatinate(II) . . . . . . . . . 13
3.2.2 Route to transplatin: from tetraamineplatinum(II) chloride . . . . . . . . . 13
4 Question 4: Chloroquine and Ferroquine 15
4.1 4(a)(i) Structure of Chloroquine . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
4.2 4(a)(ii) Structure of Ferroquine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
Page 1 of 18
,UNISA | CHE3701 Platinum Complexes and DNA Interaction
4.3 4(b) Effect of the Iron-Containing Group . . . . . . . . . . . . . . . . . . . . . . . 16
Reference List 18
Page 2 of 18
, UNISA | CHE3701 Platinum Complexes and DNA Interaction
Question 1: Platinum Complexes
1(a)(i) Chemical Properties of Pt(II) and Pt(IV)
Discuss the chemical properties of platinum(II) and platinum(IV), comparing their elec-
tronic configuration, geometry, stability and reactivity.
Platinum(II) is a d8 metal centre. The eight d electrons occupy the lower-lying dxz , dyz , dz 2 and
dxy orbitals, leaving the high-energy dx2 −y2 orbital empty. Because this orbital points directly
at the four incoming ligands, a square-planar, four-coordinate geometry is strongly favoured,
with dsp2 hybridisation and bond angles of 90◦ . This arrangement leaves the axial positions
above and below the plane open, so square-planar Pt(II) complexes are coordinatively unsatu-
rated and kinetically labile: they undergo associative (SN 2-type) ligand-substitution reactions
readily, proceeding through a five-coordinate trigonal-bipyramidal transition state. This lability
is what allows Pt(II) drugs such as cisplatin to aquate inside the cell and bind covalently to
DNA.
Platinum(IV) is a d6 metal centre and adopts an octahedral, six-coordinate geometry with
d2 sp3 hybridisation. All six d electrons pair up in the three lower-energy t2g orbitals (dxy , dxz ,
dyz ), giving a low-spin, substitutionally inert configuration. Ligand exchange at Pt(IV) is ex-
tremely slow because all six coordination sites are already occupied and no low-energy asso-
ciative pathway is available; the complex must first be reduced to Pt(II) before substitution
can occur readily. This kinetic inertness is pharmacologically useful: Pt(IV) complexes such
as satraplatin are administered as prodrugs that survive the gut and bloodstream intact, and
are reduced intracellularly by ascorbate or glutathione to release the active, ligand-labile Pt(II)
species with loss of the two axial ligands.
In summary, Pt(II) is square planar, kinetically labile and directly cytotoxic, while Pt(IV) is
octahedral, kinetically inert and biologically activated only after in vivo reduction. Pt(IV) com-
plexes are also generally more resistant to oxidation (they are already in a higher, more stable
oxidation state for platinum), whereas Pt(II) is comparatively easily oxidised back to Pt(IV) by
cellular oxidants, a property that is deliberately exploited in prodrug design (Miessler, Fischer
and Tarr, 2014).
Page 3 of 18
