Sigma-aromaticity and sigma-antiaromaticity in saturated inorganic rings

The magnetic properties of a series of inorganic saturated rings, (SiH2)n, (GeH2)n, (NH)n, (PH)n, (AsH)n, On, Sn, and Sen (n = 3-6), exhibit zigzag behavior with ring size resembling that of aromatic and antiaromatic Hückel pi-systems and (CH2)n rings. Computed GIAO-SCF nucleus-independent chemical shifts (NICS) and localized (LMO) NICS analysis indicate that the sigma-ring electrons are chiefly responsible for this zigzag behavior. This evidence for sigma-aromaticity is further supported by theoretical strain energy (TSE). The Hückel 4n + 2/4n aromaticity/antiaromaticity rule for pi-electron systems applies well to the smaller saturated rings.     

Doubly charged ion mass spectra: VI—Amines

Doubly charged ion mass spectra of 22 amines (2–10 carbon atoms) were determined using an Hitachi RMU-7L double focusing mass spectrometer. Molecular ions were not observed in the spectra of aliphatic amines. The most intense product ion peaks in the spectra of lower molecular weight amines resulted from hydrogen elimination from the molecular ion; however, as amine molecular weight increased the largest peaks resulted from both hydrogen and heavy atom elimination from the molecular ion. Dominant ions in the doubly charged ion spectra of lower molecular weight aliphatic amines were from reactions of [C_nH₃N]²⁺ (n:=2, 3, 4) type ions. The spectra of higher molecular weight aliphatic amines spanned a wide mass range. Appearance energies for some of the more prominent ions were measured in the range from 25 to 49 eV. A geometry optimized quantum mechanical self-consistent field molecular orbital treatment was used to compute the energies and structural parameters of prominent ions in the doubly charged ion mass spectra.     

Doubly-charged ethane ions: Solution to the dilemma of stability predicted by theory and instability observed in experiment

Potential energy curves have been computed for [C₂H₆]²⁺ ions and the results used to interpret the conspicuous absence of these ions in 2E mass spectra and in charge-stripping experiments. The energies and structures of geometry-optimized ground-state singlet and excited-state triplet [C₂H₆]²⁺ ions have been determined along with energies for different decomposition barriers and dissociation asymptotes. Although singlet and triplet [C₂H₆]²⁺ ions can exist as stable entities, they possess low energy barriers to decomposition. Vertical Franck-Condon transitions, involving electron impact ionization of ethane as well as charge-stripping collisions of [C₂H₆]⁺ ions, produce [C₂H₆]²⁺ ions which promptly dissociate since they are formed with energies in excess of various decomposition barriers. Appearance energies computed for doubly-charged ethane fragment ions are in accordance with experimental values.     

Novel methyl helianthrones as photosensitizers: synthesis and biological evaluation

A combination of light, oxygen and a photosensitizer is used to induce death of cancer cells by photodynamic therapy. In this study, we have synthesized several new methyl helianthrone derivatives and compared their phototoxicity with that of hypericin. In contrast to hypericin, methyl helianthrones are soluble in aqueous solutions and have a broad range of light absorbance, which allows the use of polychromatic light. Structural modifications of methyl helianthrone demonstrated that substitution of hydrogen atoms of methyl helianthrone at Positions 2 and 5 with Br atoms or methylation of its phenolic hydroxyls, significantly increases the corresponding singlet oxygen quantum yield and their phototoxicity toward alphaT3-1, M2R and LNCaP cells. The phototoxicity of some of these compounds was similar to that of hypericin. Methyl helianthrones, like hypericin, accumulated mainly in the perinuclear region as evident by confocal microscopy. Irradiation of cells pretreated with methyl helianthrone derivatives generates intracellular reactive oxygen species and lipid free radicals, as shown by a fluorescentic probe and electron paramagnetic resonance methods, respectively. The phototoxicity of these methyl helianthrones as well as their ability to oxidize membrane lipids were significantly decreased on addition of specific Type-II inhibitors, suggesting the involvement of singlet oxygen as the main oxidant.     

Inhibition of folylpolyglutamate synthetase by substrate analogues with an ornithine side chain

N^α-[4-[[(4-Aminopteridin-6-yl)methyl]amino]benzoyl]-L-ornithine (dAPA-Orn) was synthesized, and its ability to inhibit folylpolyglutamate synthetase from mouse liver was compared with that of the corresponding 2,4-diamino analogue APA-Orn. Also compared were the inhibitory activities of the deaza analogues 5-deazaAPA-Orn, 8-deazaAPA-Orn, and 5,8-dideazaAPA-Orn, as well as those of N^α-pteroyl-L-ornithine (PteOrn) and its deaza analogues 5-deazaPteOrn and 5,8-dideazaPteOrn. The inhibition constant K_i of dAPA-Orn was 7-fold greater than that of APA-Orn, indicating that the 2-amino group plays a role in binding to the active site. The binding affinity of the 2,4-diamino compounds increased in the order 5-deazaAPA < APA-Orn <5,8-dideazaAPA-Orn < 8-deazaAPA-Orn, and that of the 2-amino-4(3H)-oxo compounds increased in the order 5-deazaPteOrn < PteOrn < 5,8-dideazaPteOrn. The most potent inhibitor of both groups was 8-deazaAPA-Orn, with a K_i of 0.018 μM, coresponding to an 8-fold and 15-fold increase in affinity relative to APA-Orn and 5-deazaAPA-Orn, respectively. The results suggest (a) that the binding of Orn-containing folylpolyglutamate synthetase inhibitors is affected to a greater degree by replacement of N⁸ by a carbon atom than it is by the corresponding change at N⁵, (b) that the effect of carbon for nitrogen replacement is greater in the 2,4-diamino derivatives than in the 2-amino-4(3H)-oxo compounds, and (c) that the 2,4-diamines are the better inhibitors. Comparison of the K_i values of the Orn-containing inhibitors with the K_m values of the corresponding glutamate-containing substrates revealed that K_m/K_i ratio can vary as much as 100-fold depending on the nature of the heterocyclic moiety, suggesting that caution should be exercised in using K_m values of known substrates to predict K_i values of putative inhibitors.     

Charge neutralization of ions from benzene

Cross-sections have been measured for the charge neutrilization if ions from benzene in kiloelectron-volt collisions with benezene target molecules. Measured values range from 65 Ų for the symmetric [C₆H₆]⁺? C₆H₆ resonant reactions to 8 Ų for [C₃H₃]⁺? C₆H₆ reactions. Cross-sections computed using a simple resonance charge transfer model compare favourably with experimental data for the symmetric reactions. The cross-sections for asymmetric reactions are smaller that those for they symmetric system and magnitudes of the asymmetric cross-sections are correlated with recombination energies of the respective ions.     

Synthesis of (pyridinyl)-1,2,4-triazolo[4,3-a]pyridines

Methods for the synthesis of (pyridinyl)-1,2,4-triazolo[4,3-a]pyridines were developed. The principal route to the required intermediate 2-chloropyridines was based on rearrangements of mono N-oxides of 2,2′-bipyridine, 2,3′-bipyridine, 3,3′-bipyridine, 2,4′-bipyridine and 4,4′-bipyridine with phosphorus oxychloride. Reaction of 3,3′-bipyridine 1-oxide or 2,2′-bipyridine 1-oxide with phosphorus oxychloride gave mixtures of chloro isomers. Reaction with acetic anhydride, 3,3′-bipyridine 1-oxide and 2,2′-bipyridine 1-oxide gave exclusively [3,3′-bipyridine]-2(1H)-one and [2,2′-bipyridine]-6(1H)-one, respectively. 1,2,4-Triazolo[4,3-a]pyridines with pyridinyl groups at the 5,6,7 and 8 positions were synthesized.     

Partial-filling affinity capillary electrophoresis

Partial-filling affinity capillary electrophoresis (PFACE) is used to examine the binding interactions between two model biological systems: D-Ala-D-Ala terminus peptides to the glycopeptide antibiotic vancomycin (Van) from Streptomyces orientalis, and arylsulfonamides to carbonic anhydrase B (CAB, EC 4.2.1.1, bovine erythrocytes). Using these two systems, modifications in the PFACE technique are demonstrated including flow-through PFACE (FTPFACE), competitive flow-through PFACE (CFTPFACE), on-column ligand synthesis PFACE (OCLSPFACE), and multiple-step ligand injection PFACE (MSLIPFACE). In PFACE small plugs of sample are injected into the capillary column and an equilibrium is established between receptor and ligand during electrophoresis. Binding constants are then obtained by Scatchard analysis using changes in the migration time of the receptor/ligand on changing the concentration of the ligand/receptor. Data demonstrating the quantitative potential of these methods are presented. This review focuses on the unique capabilities of the different PFACE techniques as applied to two model biological systems.     

On the viability of small endohedral hydrocarbon cage complexes: X@C4H4, X@C8H8, X@C8H14, X@C10H16, X@C12H12, AND X@C16H16

Small hydrocarbon complexes (X@cage) incorporating cage-centered endohedral atoms and ions (X = H(+), H, He, Ne, Ar, Li(0,+), Be(0,+,2+), Na(0,+), Mg(0,+,2+)) have been studied at the B3LYP/6-31G(d) hybrid HF/DFT level of theory. No tetrahedrane (C(4)H(4), T(d)()) endohedral complexes are minima, not even with the very small hydrogen atom or beryllium dication. Cubane (C(8)H(8), O(h)()) and bicyclo[2.2.2]octane (C(8)H(14), D(3)(h)()) minima are limited to encapsulating species smaller than Ne and Na(+). Despite its intermediate size, adamantane (C(10)H(16), T(d)()) can enclose a wide variety of endohedral atoms and ions including H, He, Ne, Li(0,+), Be(0,+,2+), Na(0,+), and Mg(2+). In contrast, the truncated tetrahedrane (C(12)H(12), T(d)()) encapsulates fewer species, while the D(4)(d)() symmetric C(16)H(16) hydrocarbon cage (see Table of Contents graphic) encapsulates all but the larger Be, Mg, and Mg(+) species. The host cages have more compact geometries when metal atoms, rather than cations, are inside. This is due to electron donation from the endohedral metals into C-C bonding and C-H antibonding cage molecular orbitals. The relative stabilities of endohedral minima are evaluated by comparing their energies (E(endo)) to the sum of their isolated components (E(inc) = E(endo) - E(cage) - E(x)) and to their exohedral isomer energies (E(isom) = E(endo) - E(exo)). Although exohedral binding is preferred to endohedral encapsulation without exception (i.e., E(isom) is always exothermic), Be(2+)@C(10)H(16) (T(d)(); -235.5 kcal/mol), Li(+)@C(12)H(12) (T(d)(); 50.2 kcal/mol), Be(2+)@C(12)H(12) (T(d)(); -181.2 kcal/mol), Mg(2+)@C(12)H(12) (T(d)(); -45.0 kcal/mol), Li(+)@C(16)H(16) (D(4)(d)(); 13.3 kcal/mol), Be(+)@C(16)H(16) (C(4)(v)(); 31.8 kcal/mol), Be(2+)@C(16)H(16) (D(4)(d)(); -239.2 kcal/mol), and Mg(2+)@C(16)H(16) (D(4)(d)(); -37.7 kcal/mol) are relatively stable as compared to experimentally known He@C(20)H(20) (I(h)()), which has an E(inc) = 37.9 kcal/mol and E(isom) = -35.4 kcal/mol. Overall, endohedral cage complexes with low parent cage strain energies, large cage internal cavity volumes, and a small, highly charged guest species are the most viable synthetic targets.     

Development of a flexible approach to Nuphar alkaloids via two enantiospecific piperidine-forming reactions

In this paper we describe the stereoselective synthesis of functionalized lactam 7 via two enantiospecific piperidine-forming techniques and its employment in a general synthetic approach to Nuphar alkaloids. Specifically, the formation of piperidine 18 by formal [3 + 3] cycloaddition and stepwise annelation processes is described; the latter technique was found to be significantly more efficient than the Pd-catalyzed TMM addition process. Finally, exploitation of the exocyclic alkene installed in the piperidine-forming reaction in the transformation of 18 to (-)-deoxynupharidine ((-)-2), (-)-castoramine ((-)-3), and (-)-nupharolutine ((-)-4) via intermediate lactam 7 is delineated.