Palladium-Mediated Hydroamination of DNA-Conjugated Aryl Alkenes.

C-N bond formation is one of the most commonly used reactions in medicinal chemistry. Herein, we report an efficient Pd-promoted hydroamination reaction between DNA-conjugated aryl alkenes and a wide scope of aliphatic amines. The described reactions are demonstrated in good to excellent conversions to furnish C (sp3)-N bonds on DNA. This DNA-compatible transformation has strong potentials for the application into DNA-encoded library synthesis.

Interaction of calf thymus DNA and glucose-based gemini cationic surfactants with different spacer length: A spectroscopy and DLS study.

The interactions between calf thymus DNA and a series of glucose-based cationic gemini surfactants 1a-1c with different spacer length, n = 4, 6 and 8, were studied by UV absorption, fluorescence spectroscopy, circular dichroism, FT-IR, dynamic light scattering and zeta potential measurements. The results showed that all the surfactants could interact with DNA efficiently. On addition of increasing concentration of the surfactants, UV absorption hypochromicity with insignificant blue shift were observed, until the DNA signal disappeared. The surfactant 1c was more efficient in the reduction of absorption intensity of DNA. According to the fluorescence quenching experiments by ethidium bromide exclusion, 1c exhibited the highest binding properties, with the binding constant at 3.25 × 108 L·mol-1. The spectroscopy study indicated that the surfactants bound with the DNA by a non-intercalative mode, mainly electrostatic interaction between the positively charged headgroups of the surfactants and negatively charged phosphate groups of DNA at low concentration, and the hydrophobic interaction among the alkyl chains at high concentration. The conformation of DNA during the interaction process could be kept B-form of DNA. For 1c, the DNA molecules can be compacted to about 103 nm in hydrodynamic diameter at 0.2 mM, while the minimum sizes of DNA were 140 nm and 133 nm, respectively, in the presence of 1a and 1b. The impact of the cationic gemini surfactants on the DNA compaction and condensation would shed light on their potential applications in gene delivery.

Exploring Aldol Reactions on DNA and Applications to Produce Diverse Structures: An Example of Expanding Chemical Space of DNA-Encoded Compounds by Diversity-Oriented Synthesis.

A DNA-encoded chemical library (DECL) is built with combinatorial chemistry, which works by bringing chemical fragments together to generate diverse structures. However, chemical diversity of DNA-encoded chemical libraries is often limited by DNA compatible synthetic reactions. This report shows a conceptual strategy to expand chemical space of DNA-encoded chemical libraries by incorporation of diversity-oriented synthesis in DECL synthesis. We developed Aldol reactions on DNA in a combinatorial way. After obtaining DNA-tagged α, ß-unsaturated ketones which represent important chemical intermediates, many distinct structures with skeletal diversities are achieved by diversity-oriented synthesis.

Interactions with ctDNA of novel sugar-based gemini cationic surfactants.

The interactions between calf thymus DNA, ctDNA, and a series of sugar-based gemini cationic surfactants with different hydrophobic chains were investigated. The surface properties of the cationic gemini surfactants were firstly examined, and then their interactions with DNA and induced condensation of DNA were studied by UV-vis, ethidium bromide exclusion assay, circular dichroism, dynamic light scattering, zeta potential and atomic force microscopy. With the increase of hydrophobic chains of the surfactants, critical micelle concentrations decreased significantly, and the interactions with DNA were remarkably strengthened, with the binding constant up to 1.95 × 107 L·mol-1 according to fluorescence quenching experiments by ethidium bromide exclusion. The gemini surfactant with hexadecyl hydrocarbon chain, 1c, exhibited the highest compaction capacity for DNA, accompanied with conformation changes, as confirmed by CD and DLS measurements. The DNA molecules could be compacted to about 140 nm in hydrodynamic diameter at 0.2 mM of 1c, and the overall shifts of the positive band and significant increase of negative molar ellipticity indicated the formation of a supramolecualr chiral order of ѱ phase in which DNA were supposed to be tightly packed.