G-Quadruplexes from Human Telomeric DNA: How Many Conformations in PEG Containing Solutions?

G-quadruplex structures are an attractive target for the development of anticancer drugs, as their formation in human telomere induces a DNA damage response followed by apoptosis in cancer cells. However, the development of new anticancer drugs by means of structural-based drug design is hampered by a lack of accurate information on the exact G-quadruplex conformation adopted by the human telomeric DNA under physiological conditions. Several groups reported that, in a molecular crowded, cell-like environment, simulated by polyethylene glycol (PEG), the human telomeric DNA adopts the parallel G-quadruplex conformation. These studies have suggested that 40% (w/v) PEG concentration induces complete structural conversion from the other known human telomeric G-quadruplex conformations to the parallel G-quadruplex, thus simplifying the high structural polymorphism existing in the absence of PEG. In this study, we demonstrate that the structural conversion to the parallel G-quadruplex is not a complete reaction at physiological temperature. We report a complete kinetic and thermodynamic characterization of the conformational transitions involving the (TTAGGG)₄TT and (TTAGGG)₈TT human telomeric DNA sequences in K⁺ solution containing PEG. Our data show that the hybrid-type and parallel conformations coexist at equilibrium in the presence of PEG at physiological temperature and the degree of the quadruplex interconversion depends on the PEG molecular weight. Further, we find that telomeric DNA folds in the parallel quadruplex in the seconds time scale, a much larger time scale than the one reported for the hybrid quadruplex folding (∼ms). The whole of our data allow us to predict the relative amount of each G-quadruplex conformation as a function of temperature and time. The effect of other crowding agents like Ficoll 400 and glycerol on the quadruplex interconversion has been also explored

Crystallization Behavior and Properties of Propylene/4-Methyl-1-pentene Copolymers from a Metallocene Catalyst

Copolymers of isotactic polypropylene (iPP) with 4-methyl-1-pentene (iPP4MP) were prepared with a highly isoselective homogeneous organometallic catalyst in a range of 4-methyl-1-pentene (4MP) concentrations between about 1.7 and 14 mol %. Crystallization from the melt at different crystallizations temperatures have been performed to study the effect of 4MP comonomeric units excluded from the crystals on the crystallization of α and γ forms. All samples crystallize in mixtures of α and γ forms, and for each sample, the fraction of γ form increases with increasing crystallization temperature to achieve a maximum value fγ(max), which depends on the 4MP concentration. Compared to the homopolymer, the maximum fractional amount of γ form fγ(max) rapidly increases with increasing 4MP content achieving the highest value of 92% at low 4MP concentration of 2.2 mol %, and decreases with a further increase of 4MP concentration. These data are compared with analogous data of the maximum amount of γ form that develops in copolymers of iPP with ethylene and butene. This allows comparing the different effects of rejection of defects from the crystals, which produces interruption of the regular propene sequences and shortening of the length of the crystallizable sequences, the inclusion of defects into crystals of α and γ forms, and the effect of the crystallization kinetics. Since 4MP comonomeric units are excluded from the crystals, the behavior of iPP4MP copolymers provides the sole interruption effect, which is highly efficient and produces the highest amount of γ form of 92% at low 4MP concentration of nearly 2 mol %. The observed decrease of fγ(max) at higher 4MP concentrations is due to the too slow crystallization rate of the γ form at these 4MP contents that induces the crystallization of the kinetically favored α form. In fact, crystals of γ forms that develop in these copolymers are highly defective and show melting temperatures lower than those of the α form and, therefore, experience low undercooling at high crystallization temperatures. These results demonstrate that in metallocene iPP copolymers containing a significant amount of constitutional defects, the crystallization of the γ form is favored because of the short regular propene sequences, whereas the crystallization of the α form is always kinetically favored

Crystallization of Propene–Pentene Isotactic Copolymers as an Indicator of the General View of the Crystallization Behavior of Isotactic Polypropylene

The crystallization from the melt in isothermal conditions of metallocene random propene–pentene isotactic copolymers (iPPC5) has been studied. All samples with pentene concentration between 0.5 and 10 mol % crystallize at any crystallization temperature in mixtures of α and γ forms of isotactic polypropylene (iPP) and the amount of γ form increases with increasing crystallization temperature up to a maximum (fγ(max)), which depends on pentene concentration. Pentene defects produce a shortening of the regular propene sequences that in turn induces crystallization of the γ form. At concentrations higher than 6–7 mol %, pentene units are incorporated to a high extent in the crystals of α and trigonal forms, which are stabilized over the γ form, and fγ(max) decreases. The maximum fraction of γ form is, therefore, related to the average length of regular propene sequences and the degree of incorporation of defects in the crystals of α and γ forms. The values of fγ(max) that develop in iPPC5 copolymers have been compared with those that develop in copolymers of iPP with ethylene (iPPC2), butene (iPPC4), and hexene (iPPC6) and in stereoirregular iPPs reported in the literature. Stereoirregular iPPs and iPPC2 copolymers give the same relationship between fγ(max) and the average length of regular propene sequences (LiPP), whereas iPPC4, iPPC5, and iPPC6 copolymers show different behaviors. In particular, iPPC5 copolymers exhibit a behavior intermediate between those of iPPC4 and iPPC6 copolymers. The relationship between fγ(max) and LiPP of iPPC5 copolymers fits perfectly between the relationships found for iPPC4 and iPPC6 copolymers, in agreement with the different types and sizes of comonomers and the different efficiencies of their interruption and inclusion effects. These data give evidence of the general view of the crystallization behavior of iPP, based on the definition of a double role exerted by defects, the interruption effect that shortens the regular propene sequences and favors crystallization of γ form, and the effect of incorporation of defects into the crystalline unit cells of α and γ forms, which favors crystallization of the form that better accommodates the defect into crystals. The relative efficiency of these two effects depends on the type and size of the defect. The different relationships between fγ(max) and LiPP are a result of the equilibrium between interruption and inclusion effects achieved by each defect and confirm that the crystallization of γ form is a perfect indicator of the length of the regular propene sequences and may provide very detailed information on the molecular structure of iPP

Mechanical Properties and Morphology of Propene–Pentene Isotactic Copolymers

The mechanical behavior of propylene–pentene isotactic copolymers synthesized with a single-center organometallic catalyst in a broad interval of pentene (Pe) concentration, from 3 to 50 mol %, is analyzed. All copolymers show flexible behavior with very high deformation at breaking. The presence and entrance of Pe counits in α and δ forms of isotactic polypropylene (iPP) transform a strong and fragile iPP homopolymer into ductile and flexible materials. The stress at yield decreases as the Pe content increases, but a different behavior has been observed for samples in the α form or in the δ form. In samples in the α form, from 3 to 8.8 mol % of Pe, the stress at yield increases as the thickness of crystalline lamellae increases, while in samples in the δ form containing higher Pe counits, it decreases as the thickness of lamellae increases and Pe content increases. Phase transition of the α form in the mesophase and crystallization of the δ form, in samples with 8–11 mol % of Pe, occur upon deformation and are correlated to the strain-hardening observed at high strain

Correction to Crystal Structure of Poly(7-heptalactone)

Correction to Crystal Structure of Poly(7-heptalactone

Synthesis, Morphology, and Crystallization Kinetics of Polyheptalactone (PHL)

Aliphatic polyesters are widely studied due to their excellent properties and low-cost production and also because, in many cases, they are biodegradable and/or recyclable. Therefore, expanding the range of available aliphatic polyesters is highly desirable. This paper reports the synthesis, morphology, and crystallization kinetics of a scarcely studied polyester, polyheptalactone (PHL). First, we synthesized the η-heptalactone monomer by the Baeyer–Villiger oxidation of cycloheptanone before several polyheptalactones of different molecular weights (in the range between 2 and 12 kDa), and low dispersities were prepared by ring-opening polymerization (ROP). The influence of molecular weight on primary nucleation rate, spherulitic growth rate, and overall crystallization rate was studied for the first time. All of these rates increased with PHL molecular weight, and they approached a plateau for the highest molecular weight samples employed here. Single crystals of PHLs were prepared for the first time, and hexagonal-shaped flat single crystals were obtained. The study of the crystallization and morphology of PHL revealed strong similarities with PCL, making PHLs very promising materials, considering their potential biodegradable character