The impact of cisplatin on cancer chemotherapy cannot be denied. Over the past 20 years, much effort has been dedicated to discover new platinum-based anticancer agents that are superior to cisplatin or its analogue, carboplatin. Most structural modifications are based on changing one or both of the ligand types coordinated to platinum. Altering the leaving group can influence tissue and intracellular distribution of the drug, whereas the carrier ligand usually determines the structure of adducts formed with DNA. DNA-Pt adducts produced by cisplatin and many of its classical analogues are almost identical, and would explain their similar patterns of tumor sensitivity and susceptibility to resistance. Recently some highly innovative design strategies have emerged, aimed at overcoming platinum resistance and/or to introduce novel mechanisms of antitumor action. Platinum compounds bearing the 1,2-diaminocyclohexane carrier ligand; and those of multinuclear Pt complexes giving rise to radically different DNA-Pt adducts, have resulted in novel anticancer agents capable of circumventing cisplatin resistance. Other strategies have focused on integrating biologically active ligands with platinum moieties intended to selectively localizing the anticancer properties. With the rapid advance in molecular biology, combined with innovation, it is possible new Pt-based anticancer agents will materialize in the near future.

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Narrowly distributed spherical poly(N-vinylcaprolactam) (PNVC) microgels were prepared by precipitation polymerization in water. The effect of both anionic (sodium dodecyl sulfate, SDS) and cationic (N-dodecylpyridinium bromide, DPB) surfactants on the swelling and shrinking of the microgels were investigated by laser light scattering (LLS). Our results showed that the microgels gradually shrank to the collapsed state when the temperature increased from 20 to ∼38 °C. The addition of anionic surfactant caused an extra swelling of the microgels and shifted the collapsing temperature higher, whereas the addition of cationic surfactant has different effects on the swelling and shrinking of the microgels prepared by using different initiators, depending on whether the decomposed fragments of the initiator are ionic or neutral. Our results clearly showed that the ionic groups introduced into polymer gels from the initiators should be taken into consideration in the study of the surfactant/gel interaction.

The volume phase transition of poly(N-isopropylacrylamide) (PNIPAM) spherical microgel particles was studied by static and dynamic laser light scattering (LLS). The results were compared with the coil-to-globule transition of individual long linear PNIPAM chains. The microgel particles have a higher transition temperature, but a less sharp phase transition, in comparison with that of long linear chains. This difference has been attributed to both the short length and the broad length distribution of the subchains inside the microgels. A combination of static and dynamic LLS results revealed that even in a highly collapsed state the microgel particles retained -70% of water and the density of the microgel networks increased from 0.021 glcm3 to -0.30 s/cm3 during the phase transition. The temperature-dependence of the NMR spin-lattice relaxation times TI of PNIPAM indicate an association between water and the CH proton on the N-isopropyl group. Our results also showed that the transition was strongly influenced by the presence of surfactant. Addition of anionic surfactant, such as sodium dodecyl sulfate (SDS), promotes the swelling of the particles and shifts the transition to a higher temperature, while the addition of a cationic surfactant, such as dodecyl pyridine bromide (DPB), has less effects on the swelling and phase transition, which has been attributed to the electron-rich amide group in PNIPAM. Moreover, a two-step phase transition was observed for the first time in the presence of SDS. The dynamic LLS results demonstrates that SDS is expelled gradually from the microgel in the first-step volume phase transition.PNIPAM microgels have been reported."-26 Tanaka ef u?'.~" demonstrated that for a spherical gel the time required for swelling or shrinking is proportional to the square of its radius, whereas for microgel particles with a smaller radius, a much faster response to its environmental change occurs. In addition, the results obtained from some studies of spherical PNIPAM microgels showed that the volume phase transition is continuous, rather than the discontinuous transition observed for bulk PNIPAM gels. This difference has been attributed to the irregular particle surface formed during the phase transition.Another important aspect of the volume phase transition of PNIPAM or hydrophobically modified PNTPAM gels is that surfactant can promotes both inter-and intra-molecular solubility 1 24 so that the transition temperature increases with increasing surfactant concentration. An association of the surfactant hydrophobic tails with the hydrophobic side groups or backbone of PNIPAM has been suggested. Recently, Khokhlov ef uL3' predicted that the interaction of a polyelectrolyte gel with an oppositely charged surfactant presents three effects: (i) At low surfactant concentration, the surfactant cannot form micelles inside the network. The gel behaves as though they are in the solution of low molecular-weight salts, shrinking slightly. (ii) At higher surfactant concentration, surfactant molecules inside t...

In this report, the conformational dependence on 13 C and 15 N shifts in nucleic acids is investigated and a series of chemical shift and structure relationships are established through (i) experimental correlations of the 13 C chemical shifts with structure parameters and (ii) ab initio quantum chemical calculations at the DFT level. Good empirical correlations between the C1′ shift and sugar conformation for the ribose group as well as between the C1′ shift and the base orientation for the deoxyribose group were established and confirmed by DFT calculations. It is demonstrated that the influence of base pairing and base stacking on the chemical shifts of sugar carbons is negligible. Except for N1 in the pyrimidine group and N9 and N3 in the purine group, we did not uncover a dependency of chemical shifts trend with base orientation on sugar conformation for most base atoms. It has also been shown that most base atoms are sensitive to base pairing. However, for those that are less base orientation dependent, they may provide an effective probe of base pairing effect. As a further test of chemical shift and structure relationships established in this study program, the structures of several RNA hairpins and a d(GGTCGG) sequence were analyzed using the chemical shift method. The result shows that important structural information, such as torsion angle constraints and base pairing information, encoded in the observed 13 C and 15 N chemical shifts may be extracted for nucleic acid structure determination. It is suggested that 13 C and 15 N chemical shift methods, with their much higher spectral dispersion than that of 1 H-based methods, are evolving to becoming a promising alternatives for the structural elucidation of nucleic acids involving a large number of residues.