Combined theoretical and computational study of interstrand DNA guanine–guanine cross-linking bytrans-[Pt(pyridine)2] derived from the photoactivated prodrugtrans,trans,trans-[Pt(N3)2(OH)2(pyridine)2]

Molecular modeling and extensive experimental studies are used to study DNA distortions induced by binding platinum(II)-containing fragments derived from cisplatin and a new class of photoactive platinum anticancer drugs. The major photoproduct of the novel platinum(IV) prodrug trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1) contains the trans-{Pt(py)2}2+ moiety. Using a tailored DNA sequence, experimental studies establish the possibility of interstrand binding of trans-{Pt(py)2}2+ (P) to guanine N7 positions on each DNA strand. Ligand field molecular mechanics (LFMM) parameters for Pt–guanine interactions are then derived and validated against a range of experimental structures from the Cambridge Structural Database, published quantum mechanics (QM)/molecular mechanics (MM) structures of model Pt–DNA systems and additional density-functional theory (DFT) studies. Ligand field molecular dynamics (LFMD) simulation protocols are developed and validated using experimentally characterized bifunctional DNA adducts involving both an intra- and an interstrand cross-link of cisplatin. We then turn to the interaction of P with the DNA duplex dodecamer, d(5′-C1C2T3C4T5C6G7T8C9T10C11C12-3′)·d(5′-G13G14A15G16A17C18G19A20G21A22G23G24-3′) which is known to form a monofunctional adduct with cis-{Pt(NH3)2(py)}. P coordinated to G7 and G19 is simulated giving a predicted bend toward the minor groove. This is widened at one end of the platinated site and deepened at the opposite end, while the P–DNA complex exhibits a global bend of 67° and an unwinding of 20°. Such cross-links offer possibilities for specific protein–DNA interactions and suggest possible mechanisms to explain the high potency of this photoactivated complex

Tetrahedral bonding in twisted bilayer graphene by carbon intercalation

Based on ab initio calculations, we study the effect of intercalating twisted bilayer graphene with carbon. Surprisingly, we find that the intercalant pulls the atoms in the two layers closer together locally when placed in certain regions in between the layers, and the process is energetically favorable as well. This arises because in these regions of the supercell, the local environment allows the intercalant to form tetrahedral bonding with nearest atoms in the layers. Intercalating AB- or AA-bilayer graphene with carbon does not produce this effect; therefore, the nontrivial effect owes its origin to both using carbon as an intercalant and using twisted bilayer graphene as the host. This opens new routes to manipulating bilayer and multilayer van der Waals heterostructures and tuning their properties in an unconventional way