RESUMEN

Designing and synthesizing flawless two-dimensional polymers (2D-Ps) via meticulous molecular preorganization presents an intriguing yet challenging frontier in research. We report here the single-crystal-to-single-crystal (SCSC) synthesis of a 2D-P via thermally induced topochemical azide-alkyne cycloaddition (TAAC) reaction. A designed monomer incorporating two azide and two alkyne units is synthesized. The azide and alkyne groups are preorganized in the monomer crystal in reactive geometries for polymerizations in two orthogonal directions. On heating, the polymerizations proceed in a hierarchical manner; at first, the monomer reacts regiospecifically in a SCSC fashion to form a 1,5-triazolyl-linked 1D polymer (1D-P), which upon further heating undergoes another SCSC polymerization to a 2D-P through a second regiospecific TAAC reaction forming 1,4-triazolyl-linkages. Two different linkages in orthogonal directions make this an architecturally attractive 2D-P, as determined, at atomic resolution, by single-crystal X-ray diffraction. The 2D-P reported here is thermally stable in view of the robust triazole-linkages and can be exfoliated as 2D-sheets.

RESUMEN

There is huge demand for developing guests that bind ß-CD and can conjugate multiple cargos for cellular delivery. We synthesized trioxaadamantane derivatives, which can conjugate up to three cargos per guest. 1 H NMR titration and isothermal titration calorimetry revealed these guests form 1 : 1 inclusion complexes with ß-CD with association constants in the order of 103  M-1 . Co-crystallization of ß-CD with guests yielded crystals of their 1 : 1 inclusion complexes as determined by single-crystal X-ray diffraction. In all cases, trioxaadamantane core is buried within the hydrophobic cavity of ß-CD and three hydroxyl groups are exposed outside. We established biocompatibility using representative candidate G4 and its inclusion complex with ß-CD (ß-CD⊂G4), by MTT assay using HeLa cells. We incubated HeLa cells with rhodamine-conjugated G4 and established cellular cargo delivery using confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS) analysis. For functional assay, we incubated HeLa cells with ß-CD-inclusion complexes of G4-derived prodrugs G6 and G7, containing one and three units of the antitumor drug (S)-(+)-camptothecin, respectively. Cells incubated with ß-CD⊂G7 displayed the highest internalization and uniform distribution of camptothecin. ß-CD⊂G7 showed higher cytotoxicity than G7, camptothecin, G6 and ß-CD⊂G6, affirming the efficiency of adamantoid derivatives in high-density loading and cargo delivery.

Asunto(s)

beta-Ciclodextrinas , Humanos , Células HeLa , beta-Ciclodextrinas/química , Cristalografía por Rayos X , Calorimetría , Camptotecina

RESUMEN

We have designed, synthesized, and crystallized 36 compounds, each containing an azide group and an oxygen atom separated by three bonds. Crystal structure analysis revealed that each of these molecules adopts a conformation in which the azide and oxygen groups orient syn to each other with a short O⋅⋅⋅Nß contact. Geometry-optimized structures [using M06-2X/6-311G(d,p) level of theory] also showed the syn conformation in all 36 of these cases, suggesting that this is not merely a crystal packing effect. Quantum topological analysis using Bader's Atoms in Molecules (AIM) theory revealed bond paths and bond critical points (BCP) in these structures suggesting its nature and energetics to be similar to weak hydrogen bonding. The NCI-RDG plot clearly revealed the attractive interaction consisting of electrostatic or dispersive components in all the 36 systems. NBO analysis suggested a weak orbital-relaxation (charge-transfer) contribution of energy for a few (sp2) O-donor systems. Natural population analysis (NPA) and molecular electrostatic potential mapping (MESP) of these crystal structures further revealed the existence of favorable azide-oxygen interaction. A CSD search indicated the frequent and consistent occurrence of this interaction and its role dictating the syn conformation of azide and oxygen in molecules where these groups are separated by 2-4 bonds.