3-Dimensional structural characterization of cationized polyhedral oligomeric silsesquioxanes (POSS) with styryl and phenylethyl capping agents

The 3-dimensional gas-phase conformations of polyhedral oligomeric silsesquioxanes (POSS), R 8 Si 8 O 12 , capped with styryl and phenylethyl substituents (R) and cationized by sodium were examined. MALDI was used to generate sodiated styryl-POSS (Na + Sty 8 T 8 ) and phenylethyl-POSS (Na + PhEt 8 T 8 ) ions and their collision cross-sections in helium were measured using ion mobility-based methods. Five distinct conformers with different collision cross-sections were experimentally observed for Na + Sty 8 T 8 while only one conformer was detected for Na + PhEt 8 T 8 . Theoretical modeling of Na + Sty 8 T 8 , using molecular mechanics/dynamics calculations, predicts three low-energy conformations. In each conformer, the Na + ion binds to four oxygens on one side of the Si-O cage and the styryl groups extend away from the cage. However, different numbers of styryl groups "pair" together (forming 2, 3 or 4 pairs), yielding three different conformations. The calculated cross-sections of these conformers match the largest three cross-sections obtained from the ion mobility experiments (â\u88¼2% error). If, however, one or two of the styryl groups are rotated so that the phenyl groups are "cis" with respect to the Si atom on the cage (i.e., the Si-C=C-C dihedral angle changes from 180 to 0 â\u80¢ ) two smaller conformers are predicted by theory whose cross-sections match the smallest two values obtained from the ion mobility experiments (1-2% error). Theoretical modeling of Na + PhEt 8 T 8 yields one low-energy conformation in which the Na + ion binds to one oxygen on the Si-O cage and is sandwiched between two phenyl groups. The remaining phenylethyl groups fold toward the Si-O cage, yielding a significantly more compact structure than Na + Sty 8 T 8 (â\u88¼20% smaller cross-section). The calculated cross-section of the predicted Na + PhEt 8 T 8 structure agrees very well with the experimental cross-section obtained from the ion mobility experiments (â\u88¼1% error)

Stabilization and structure of telomeric and c-myc region intramolecular G-quadruplexes: The role of central cations and small planar ligands

A promising approach for anticancer strategies is the stabilization of telomeric DNA into a G-quadruplex structure. To explore the intrinsic stabilization of folded G-quadruplexes, we combined electrospray ionization mass spectrometry, ion mobility spectrometry, and molecular modeling studies to study different DNA sequences known to form quadruplexes. Two telomeric DNA sequences of different lengths and two DNA sequences derived from the NHE III1 region of the c-myc oncogene (Pu22 and Pu27) were studied. NH4+ and the ligands PIPER, TMPyP4, and the three quinacridines MMQ1, MMQ3, and BOQ1 were complexed with the DNA sequences to determine their effect on the stability of the G-quadruplexes. Our results demonstrate that G-quadruplex intramolecular folds are stabilized by NH4+ cations and the ligands listed. Furthermore, the ligands can be classified according to their ability to stabilize the quadruplexes and end stacking is shown to be the dominant mode for ligand attachment. In all cases our solvent-free experimental observations and theoretical modeling reveal structures that are highly relevant to the solution-phase structures

G-Quadruplex DNA Assemblies: Loop Length, Cation Identity, and Multimer Formation

G-rich DNA sequences are able to fold into structures called G-quadruplexes. To obtain general trends in the influence of loop length on the structure and stability of G-quadruplex structures, we studied oligodeoxynucleotides with random bases in the loops. Sequences studied are dGGGWiGGGWjGGGWkGGG, with W = thymine or adenine with equal probability, and i, j, and k comprised between 1 and 4. All were studied by circular dichroism, native gel electrophoresis, UV-monitored thermal denaturation, and electrospray mass spectrometry, in the presence of 150 mM potassium, sodium, or ammonium cations. Parallel conformations are favored by sequences with short loops, but we also found that sequences with short loops form very stable multimeric quadruplexes, even at low strand concentration. Mass spectrometry reveals the formation of dimers and trimers. When the loop length increases, preferred quadruplex conformations tend to be more intramolecular and antiparallel. The nature of the cation also has an influence on the adopted structures, with K+ inducing more parallel multimers than NH4+ and Na+. Structural possibilities are discussed for the new quadruplex higher-order assemblies