Water-soluble camptothecin derivatives that are intrinsic topoisomerase I poisons

[structure: see text] In an effort to improve the water solubility of camptothecin, four 20-O-phosphate and phosphonate analogues have been prepared. These analogues are freely water soluble, stable at physiological pH, and stabilize the human topoisomerase I-DNA covalent binary complex with the same sequence selectivity as camptothecin itself. All four compounds inhibited the growth of yeast expressing human topoisomerase I in an enzyme-dependent fashion.     

A discussion on mean excess plots

The mean excess plot is a tool widely used in the study of risk, insurance and extreme values. One use is in validating a generalized Pareto model for the excess distribution. This paper investigates some theoretical and practical aspects of the use of the mean excess plot.     

Fingerprint analysis and the application of HPTLC to the determination of identity and quality of botanicals, from an industry perspective

There are many examples of botanical identity methodology currently in use today; all have associated levels of confidence and, hence, application for their intended purpose. This paper addresses the application of some of these methods to identify and qualify commonly traded herbs. The relevance of botanical identity and quality within the dietary supplement industry has seen a dramatic increase in the last several years, and now with the current Good Manufacturing Practices (cGMPs) recently published and the requirement for 100% identity testing, there is an increased need for reliable methods of analysis and subsequent interpretation of the results or data derived from these methods, given the diversity of samples and matrixes seen on a daily basis in a commercial setting. Example applications of methods described herein illustrate how one can confidently and effectively satisfy the 100% identity rule of the cGMPs to identify crude raw materials and their powdered or liquid extracts as well as identify a majority of such ingredients in finished products with diverse matrixes. The three techniques discussed in this paper are viewed from a qualitative perspective with primary emphasis on the application of HPTLC to a variety of complex samples with varying degrees of difficulty of analysis and interpretation. The three methods discussed are (1) HPTLC, for its fingerprint/pattern recognition capabilities as well as marker compound analysis; (2) microscopy, for identification/recognition of unique cellular, anatomic features and characteristics of the target plant or adulterants; and (3) HPLC for marker compound identification, quantitation, and/or other fingerprint qualities it may contribute to the data set. To support the applications and methods described herein, this paper presents four key approaches to assist in the interpretation of the data collected in order to correctly determine the identity of botanicals and their powdered extracts: the "marker approach," the "multicomponent-based approach", the "pattern approach," and the "multipattern approach", and how these approaches can be used with a vanguard/rearguard strategy in analytical testing as well as forming a basis for the "functional fingerprint" and the concept of phytoequivalence.     

Breakup of air bubbles in water: memory and breakdown of cylindrical symmetry

Using high-speed video, we have studied air bubbles detaching from an underwater nozzle. As a bubble distorts, it forms a thin neck which develops a singular shape as it pinches off. As in other singularities, the minimum neck radius scales with the time until the breakup. However, because the air-water interfacial tension does not drive the breakup, even small initial cylindrical asymmetries are preserved throughout the collapse. This novel, nonuniversal singularity retains a memory of the nozzle shape, size, and tilt angle. In the last stages, the air appears to tear instead of pinch.     

Three-dimensional shear in granular flow

The evolution of granular shear flow is investigated as a function of height in a split-bottom Couette cell. Using particle tracking, magnetic-resonance imaging, and large-scale simulations, we find a transition in the nature of the shear as a characteristic height H* is exceeded. Below H* there is a central stationary core; above H* we observe the onset of additional axial shear associated with torsional failure. Radial and axial shear profiles are qualitatively different: the radial extent is wide and increases with height, while the axial width remains narrow and fixed.     

Asymptotic Lower Bound for the Relative Disparities of Truncated-Path-Integral Partition Functions

Any truncated-path-integral partition function of a nonrelativistic quantum system in thermodynamic equilibrium—one obtained by means of the Feynman path-integral-procedure using a finite number of such integrals—is known to have a value not less than that of the exact one corresponding to it. A rigorous asymptotic lower bound obtained for the relative disparity in their values—the difference in their values divided by that of the exact partition function— confirms asymptotic positive-definiteness of the original upper bound. Values determined directly for a linear harmonic oscillator agree asymptotically with values of they bound.     

Preparation and Electrophilic Substitution of 1-Trimethylsilylpentadienyllithium

Pentadienyllithium (16) was regioselectively and efficiently transformed to 1-trimethylsilyl-2,4-pentadiene (17) by reaction with chlorotrimethylsilane (Scheme 5). Deprotonation of 17 and subsequent electrophilic attack furnished the regioisomeric products 12 and/or 13 in good yields (Schemes 5 and 6). The utility of the reaction 18 → 12 for the convergent assembly of the 1-silyl-1,3-butadiene unit with an olefinic dienophile is further illustrated by the smooth intramolecular Diels-Alder reaction 19 → 20 .     

Promoting effect of ionic liquids on ligand substitution reactions

Ionic liquid solvents N-hexylpyridinium bistrifylimide ([C₆pyr][Tf₂N]] and 1-butyl-3-methylimidazolium hexafluorophosphate ([C₄mim][PF₆]) promoted the displacement of anionic ligands by pyridine derivatives in trans-(Ph₃P)₂Rh(CO)NO₃ to a much greater extent than did dichloromethane. Thus, addition of a slight excess of 2-fluoropyridine to trans-(Ph₃P)₂Rh(CO)NO₃ in [C₄mim][PF₆] gave a 29:71 product mixture of trans-(Ph₃P)₂Rh(CO)NO₃:[trans-(Ph₃P)₂Rh(CO)(2-fluoropyridine)][NO₃], while the ratio was 91:9 in dichloromethane.