Permeability- and Surface-Energy-Tunable Polyurethane Acrylate Molds for Capillary Force Lithography

A permeability- and surface-energy-controllable polyurethane acrylate (PUA) mold, a “capillary-force material (CFM)” mold, is introduced for capillary-force lithography (CFL). In CFL, the surface energy and gas permeability of the mold are crucial. However, the modulation of these two main factors at a time is difficult. Here, we introduce new CFM molds in which the surface energy and permeability can be modified by controlling the degree of cross-linking of the CFM. As the degree of cross-linking of the CFM mold increases, the surface energy and air permeability decrease. The high average functionality of the mold material makes it possible to produce patterns relatively finely and rapidly due to the high rate of capillary rise and stiffness, and the low functionality allows for patterns to form on a curved surface with conformal contact. CFMs with different functionality and controllable-interfacial properties will extend the capabilities of capillary force lithography to overcome the geometric limitations of patterning on a scale below 100 nm and micro- and nanopatterning on the curved region

Binding of Daunomycin to Diaminopurine- and/or Inosine-Substituted DNA^†^,^‡

The binding of the anticancer drug daunomycin to double-helical DNA has been investigated by DNase I footprinting and fluorescence titration, using a series of polymerase chain reaction (PCR) synthesized DNA fragments that contained systematic base substitutions to alter the disposition of functional groups within the minor groove. The 160 bp tyrT DNA fragment constituted the starting material. Fragments in which (i) inosine was substituted for guanosine, (ii) diaminopurine was substituted for adenine, and (iii) both inosine and diaminopurine were substituted for guanosine and adenine, respectively, were studied. These fragments permit the role of the 2-amino group in the minor groove to be systematically explored. The results of DNase I footprinting experiments confirmed that daunomycin binds preferentially to 5‘(A/T)GC and 5‘(A/T)CG triplets in the normal fragment. Substitution of inosine for guanosine, with the concomitant loss of the N-2 in the minor groove, weakened binding affinity but did not dramatically alter the sequence preference associated with daunomycin binding. Complete reversal of the location of the N-2 group by the double substitution, however, completely altered the sequence preference of daunomycin and shifted its binding from the canonical triplets to ones with a 5‘IDD motif. These results have critically tested and confirmed the proposed key roles of the daunosamine moiety and the 9-OH group of daunomycin in dictating binding to preferred sites. In a parallel study, both macroscopic and microscopic binding to the normal tyrT fragment were investigated, experiments made possible by using PCR to prepare large quantities of the long, defined DNA sequence. The results of these experiments underscored the complexity of the interaction of the drug with the DNA lattice and revealed unequivocal heterogeneity in its affinity for different binding sites. A class of high-affinity sites, most probably corresponding to the 5‘(A/T)GC and 5‘(A/T)CG triplets, was identified and characterized in macroscopic binding isotherms

Parsing the Free Energy of Anthracycline Antibiotic Binding to DNA^†

The DNA binding free energy of eight anthracycline antibiotics was determined as a function of NaCl concentration. Compounds were chosen for study that differed from the parent compounds, doxorubicin or daunorubicin, at a single chemical substituent. Determination of the salt concentration dependence of the binding constant allowed us to dissect the DNA binding free energy of each compound into its component nonelectrostatic and polyelectrolyte contributions. Comparison of the nonelectrostatic free energy contribution allowed us to evaluate the net energetic contribution of specific functional groups to DNA binding. These quantitative data revealed a surprisingly large and favorable energetic contribution (2 kcal mol-1) of the groove-binding daunosamine moiety and a substantial energetic penalty for alteration of its stereochemistry. The energetic cost of removal of hydroxyl groups at the C-9 and C-14 positions (which structural studies indicate may participate in hydrogen-bonding interactions with the DNA) was approximately 1 kcal mol-1. Replacement of the 3‘-amino group with a hydroxyl group led to a loss of 0.7 kcal mol-1 in binding free energy, above and beyond the energetic penalty resulting from the removal of its positive charge from the antibiotic. The results and analysis presented here provide a rigorous and detailed description of structure−DNA affinity relationships among anthracycline antibiotics. The results are of general interest in understanding how total ligand binding free energies are partitioned among substituents and will be useful in the formulation of rules for the rational design of novel DNA binding agents