Nanoindentation as a Probe for Mechanically‐Induced Molecular Migration in Layered Organic Donor–Acceptor Complexes

Nanoindentation and scratch experiments on 1:1 donor–acceptor complexes, 1 and 2 , of 1,2,4,5‐tetracyanobenzene with pyrene and phenanthrene, respectively, reveal long‐range molecular layer gliding and large interaction anisotropy. Due to the layered arrangements in these crystals, these experiments that apply stress in particular directions result in the breaking of interlayer interactions, thus allowing molecular sheets to glide over one another with ease. Complex 1 has a layered crystal packing wherein the layers are 68° skew under the (002) face and the interlayer space is stabilized by van der Waals interactions. Upon indenting this surface with a Berkovich tip, pile‐up of material was observed on just one side of the indenter due to the close angular alignment of the layers with the half angle of the indenter tip (65.35°). The interfacial differences in the elastic modulus (21 %) and hardness (16 %) demonstrate the anisotropic nature of crystal packing. In 2 , the molecular stacks are arranged in a staggered manner; there is no layer arrangement, and the interlayer stabilization involves C? H???N hydrogen bonds and π???π interactions. This results in a higher modulus (20 %) for (020) as compared to (001), although the anisotropy in hardness is minimal (4 %). The anisotropy within a face was analyzed using AFM image scans and the coefficient of friction of four orthogonal nanoscratches on the cleavage planes of 1 and 2 . A higher friction coefficient was obtained for 2 as compared to 1 even in the cleavage direction due to the presence of hydrogen bonds in the interlayer region making the tip movement more hindered.     

The Thermodynamics of Translesion DNA Synthesis Past Major Adducts of Enantiomeric Analogues of Antitumor Cisplatin

The Pt^II-coordination complex [PtCl₂(DAB)] (DAB=2,3-diaminobutane) belongs to a class of cytotoxic cisplatin analogues that contain chiral diamine ligands. Enantiomeric pairs of these compounds have attracted particular interest because they have different effects on different DNA conformations, which, in turn, influences the binding of damaged-DNA-processing enzymes that control downstream effects of the adducts, and thus exhibit different biological activities of the enantiomers. Herein, we studied the translesion synthesis across the major 1,2-d(GG) intrastrand cross-link formed by the R,R and S,S enantiomers of [Pt(DAB)]²⁺ in the TGGT sequence by using the enzyme that catalyzes the polymerization of deoxyribonucleotides into a DNA strand. We also employed differential scanning calorimetry (DSC) to measure the thermodynamic changes associated with replication-bypass past 1,2-d(GG) adducts of the [Pt(DAB)]²⁺ enantiomers. In the sequence TGGT, the 1,2-d(GG) intrastrand cross-links that were formed by the enantiomeric pairs of [Pt(DAB)]²⁺ inhibited DNA polymerization in a chirality-dependent manner. The thermodynamic data helped to understand the effect of the alterations in thermodynamic stability of DNA caused by the Pt-d(GG) adducts upon DNA polymerization across these lesions. Moreover, these data can possibly explain the influence of these alterations on the ability of many DNA polymerases to bypass adducts of antitumor platinum drugs. These results also highlighted the usefulness of DSC in evaluating the impact of DNA adducts of platinum-coordinated compounds on the processing of these lesions by damaged-DNA processing-enzymes.