Platinum(IV) complexes are usually inert and stable compounds which can be photoactive pro-drugs to produce Pt(II) species with promising anti-cancer activity. Studies of the photochemistry of Pt(IV) complexes by time-dependent density functional theory (TDDFT) and spectroscopic methods show close agreement. Broad exploration of cis/trans geometries, trans influences, the nature of the OR− and (pseudo)halogen ligands, electron-withdrawing/donating/ delocalizing substituents on the N-ligands, and intramolecular H-bonds shows that (1) the design of platinum(IV) complexes with intense bands shifted towards longer wavelengths (~330 nm) can be achieved by introducing intramolecular Hbonds involving the OH ligands and 2-hydroxyquinoline or by iodido ligands, (2) mesomeric electron-withdrawing substituents on pyridine result in low-energy absorption with significant intensity in the visible region, and (3) the distinct makeup of the molecular orbitals in electronic transitions for cis/trans-{Pt(N3)2} isomers result in different photoproducts. In general, the comparison of the optimised geometries shows that Pt(IV) complexes with longer Pt−L bonds are more likely to undergo photoreduction with longer-wavelength light. Complex trans, trans, trans-[Pt(N3)2(OH)2(NH3)(4-nitropyridine)] was first synthesised. The experimental UV-Vis spectrum in aqueous solution correlates well with the intense band in the computed spectrum whereas the overlay in the low-energy absorption region can be improved by a solvent model. This combined computational and experimental study shows that TDDFT can be a design tool to tune the coordination environment for optimizing photoactive Pt(IV) compounds as anticancer agents without immediate need for synthesis. Additionally, molecular modeling is used to study DNA distortions induced by binding metal-containing fragments derived from cisdiamminodichloroplatinum( II) (cisplatin) and a new class of photoactive platinum anticancer drugs. Ligand field molecular mechanics (LFMM) parameters for Pt– guanine interactions are derived and validated against a range of experimental structures from the Cambridge Structural Database, published quantum mechanics/molecular mechanics (QM/MM) structures of model Pt-DNA systems and additional DFT studies. LFMM gives a good description of the local Ptguanine coordination at a fraction of the computational cost of QM/MM methods. The force field is then used to develop protocols for ligand field molecular dynamics (LFMD) simulations using experimentally characterised bifunctional DNA adducts involving both an intra- and an interstrand crosslink of cisplatin as a prelude to studying the interaction of trans-{Pt(py)2}2+ (P, py = pyridine), the major photoproduct of the novel platinum(IV) complex trans,trans,trans- [Pt(N3)2(OH)2(py)2] (17), with the DNA duplex dodecamer, d(C1C2T3C4T5C6G7T8C9T10C11C12)• d(G13G14A15G16A17C18G19A20G21A22G23G24). Based on the observed formation of a trans species when 17 is photoreduced in the presence of 5’-guanosine monophosphate plus the major-groove binding mode of the monofunctional complex cis-{Pt(NH3)2(py)}2+, P is proposed to coordinate to G7 and G19. This P-DNA adduct has a widened minor groove at one end of the platinated site and deepened minor groove at the opposite end, and exhibits a global bend of ~67° and an unwinding of ~20°. Brabec et al. subsequently demonstrated experimentally that such interstrand GG crosslinks can form as a result of the photoactivation of 17 in the presence of DNA. Such cross-links offer possibilities for specific protein–DNA interactions and suggest possible mechanisms to explain the high potency of this photoactivated complex.