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A new approach is presented to evaluate the molecular strain and bonding behavior in strained organic molecules on the basis of the electrostatic theorem of Hellmann−Feynman through the force concept instead of energetics. Taking advantage of the physical simplicity, visuality, and quantification of this model, chemically meaningful definitions of equivalent point charge, overlap force angle, strain force, binding force, tension energy, and the bond force angle have been proposed to measure the molecular strain, bent bonds, and bonding behavior of strained organic molecules at the HF/6-31G* level of theory. The overlap force angles are consistent with the experiment and other ab initio molecular orbital calculations. Results reveal that the overlap force angle, strain force, tension energy, and bond force angle can be used to account for the relative stabilities of small propellanes. The magnitude of binding force suggests the existence of central bonds in small propellanes. The bond force angles in most strained organic molecules seem to prefer the tetrahedral angle 109.5°, while those in three-membered rings prefer the angle 120° over the angle 109.5°, though the geometrical angles can largely range from 60° to 132°. This indicates that, in most cases, the atomic orbitals have to be overlapped in the manner of the ideal or nearly ideal tetrahedral hybrid in order to relax the molecular strain. The largely shifted overlapping charge outside rings and bond force angles of nearly 120° for HCH, HCC, and CCC and the resultant increased s character of C−H bond for three-membered rings can rationalize the C−C bond's higher reactivity than the C−C bonds of other rings. In general, the departure (Δβ) of the bond force angle from the tetrahedral angle provides a measure of the degree of relaxation of the charge density from the geometrical constraints imposed by the nuclear framework and may be used as a way of assessing the molecular strain, reactivity, and stability for strained organic molecules.

The reactions of two N/O mixed-donor crown ethers, 1,12,15-triaza-3,4:9,10-dibenzo-5,8-dioxacycloheptadecane (OenNdienH4) and 1,12-diaza-3,4:9,10-dibenzo-5,8-dioxacyclopentadecane (OenNtnH4) with MMe3 (M = Al, Ga) are reported. OenNdienH4 reacted with 3 equiv of AlMe3 to form (AlMe)(AlMe2)(OenNdienH4)(AlMe3) (1) which contains three different MenAl groups:  AlMe, AlMe2, AlMe3. OenNtnH4 reacted with 2 equiv of AlMe3 to afford (AlMe2)(OenNtnH4)(AlMe3) (2) containing two chemically inequivalent aluminum centers. However, the reaction of OenNdienH4 with GaMe3 in 1:3 ratio resulted in (OenNdienH4)2(GaMe2OH)4 (3). The (Me2GaOH)4 component contains an eight-membered Ga−O ring linked via four hydrogen bonds to two molecules of OenNdienH4 which interacts from opposite sides of the Ga4O4 ring. The reaction of OenNtnH4 with GaMe3 in 1:2 ratio produced (OenNtnH4)(GaMe2OH)3 (4), a one-dimensional hydrogen bonded system which incorporates one OenNtnH4 ligand and one nonplanar six-membered ring with alternating Ga and O atoms (GaMe2OH)3.

He I and He II photoelectron spectra of several isomeric ethynyl- and diethynylpyridines have been measured. The spectra were analyzed with the aid of empirical arguments:  relative band intensities and comparison with spectra of related compounds (ethynylbenzenes). AM1 calculations were also performed to confirm the assignment. We have deduced for the first time, solely on empirical grounds, the presence of orbital interactions between nitrogen lone pairs and in-plane π-orbitals of the ethynyl group. Relative Lewis basicities are predicted and rationalized.

Using a chemiluminescence immunoassay, paromomycin and lasalocid were shown to inhibit Cryptosporidium parvum growth in Madin-Darby canine kidney cells in a concentration-dependent manner. The median effective concentrations (EC50s) for paromomycin and lasalocid were 1184 mg/L and 0.4 mg/L, respectively. Neither drug was cytotoxic to host cells at concentrations up to five times their EC50s. Drug combination studies were conducted and the resulting data were analysed by the median-effect principle and combination index method. Statistically significant synergy was observed when combinations of paromomycin and lasalocid were used at ratios of 5000:1 and 2500:1. A possible mechanism for synergy is discussed.

Cryptosporidial infections in severe combined immune deficient (SCID) mice produce a chronic disease state which in the later stages leads to extraintestinal involvement and hepatic dysfunction. To further characterize the infection dynamics in this model and monitor the changes in the hepatic system, a dose titration of the oocyst inoculum was performed and alkaline phosphatase levels in the sera were assayed. Ten SCID mice per dose were inoculated with 10(3), 10(4), 10(5), 10(6), or 10(7) oocysts. Oocyst shedding in the feces was quantified by microscopic enumeration. Mice inoculated with 10(6) oocysts and those inoculated with 10(7) oocysts demonstrated similar oocyst shedding patterns, but the 10(7)-oocyst group exhibited signs of distress (e.g., weight loss and icterus) earlier. The intensity of the infection increased markedly approximately 14 days postinoculation (p.i.) and continued to increase steadily over the next 6 weeks. Inoculation with lower oocyst doses produced a delay in patency (e.g., it occurred 7 days later with the 10(5)-oocyst inoculum and 14 days later with the 10(4)-oocyst inoculum). Mean serum alkaline phosphatase levels in the 10(7)-oocyst group were more than twice control values at 5 weeks p.i. and continued to increase over the next 8 weeks. Oocyst doses and alkaline phosphatase levels were positively correlated with hepatobiliary colonization (r = 0.71) and liver necrosis (r = 0.65) at 13 weeks p.i. A strong positive correlation between hepatobiliary colonization and liver necrosis at 13 weeks p.i. (r = 0.87) was observed.

The UL5, UL8, and UL52 genes of herpes simplex virus type 1 encode a multisubunit assembly that possesses primase, DNA helicase, and DNA-dependent nucleoside triphosphatase activities. A subassembly consisting of the UL5 and UL52 gene products retains these activities. The nucleoside triphosphatase activity of the UL5/UL52 subassembly is strongly stimulated by both homo- and heteropolymeric single-stranded DNA. Double-stranded DNA has little ability to stimulate the ATPase activity. The subassembly binds both double and single-stranded DNA. Nucleotides are not required for DNA-binding. The minimum length of single-stranded DNA that is bound and that stimulates enzymatic activity is about 12 nucleotides. The kinetic parameters of the ATPase activity of the subassembly are affected by the length of the oligonucleotide coeffector. The Km decreases as the coeffector length is increased up to a length of about 20 nucleotides and then remains independent of coeffector length. The first order rate constant for ATPase activity exhibits a quasihyperbolic dependence on the length of the DNA coeffector and is maximal for coeffectors of 20 nucleotides and longer.