Guanosine Nucleolipids: Synthesis, Characterization, Aggregation and X-Ray Crystallographic Identification of Electricity-Conducting G-Ribbons

Abstract

The lipophilization of beta -d-riboguanosine (1) with various symmetric as well as asymmetric ketones is described (-> 3a-3f). The formation of the corresponding O-2 ` ,3 ` -ketals is accompanied by the appearance of various fluorescent by-products which were isolated chromatographically as mixtures and tentatively analyzed by ESI-MS spectrometry. The mainly formed guanosine nucleolipids were isolated and characterized by elemental analyses, H-1-, C-13-NMR and UV spectroscopy. For a drug profiling, static topological polar surface areas as well as (10)logP(OW) values were calculated by an increment-based method as well as experimentally for the systems 1-octanol-H2O and cyclohexane-H2O. The guanosine-O-2 ` ,3 ` -ketal derivatives 3b and 3a could be crystallized in (D-6)DMSO - the latter after one year of standing at ambient temperature. X-ray analysis revealed the formation of self-assembled ribbons consisting of two structurally similar 3b nucleolipid conformers as well as integrated (D-6)DMSO molecules. In the case of 3a.DMSO, the ribbon is formed by a single type of guanosine nucleolipid molecules. The crystalline material 3b.DMSO was further analyzed by differential scanning calorimetry (DSC) and temperature-dependent polarization microscopy. Crystallization was also performed on interdigitated electrodes (Au, distance, 5 mu m) and visualized by scanning electron microscopy. Resistance and amperage measurements clearly demonstrate that the electrode-bridging 3b crystals are electrically conducting. All O-2 ` ,3 ` -guanosine ketals were tested on their cytostatic/cytotoxic activity towards phorbol 12-myristate 13-acetate (PMA)-differentiated human THP-1 macrophages as well as against human astrocytoma/oligodendroglioma GOS-3 cells and against rat malignant neuroectodermal BT4Ca cells.