1659-75-2Relevant academic research and scientific papers
New ultrahigh affinity host-guest complexes of cucurbit[7]uril with bicyclo[2.2.2]octane and adamantane guests: Thermodynamic analysis and evaluation of M2 affinity calculations
Moghaddam, Sarvin,Yang, Cheng,Rekharsky, Mikhail,Ko, Young Ho,Kim, Kimoon,Inoue, Yoshihisa,Gilson, Michael K.
, p. 3570 - 3581 (2011)
A dicationic ferrocene derivative has previously been shown to bind cucurbit[7]uril (CB[7]) in water with ultrahigh affinity (ΔGo= -21 kcal/mol). Here, we describe new compounds that bind aqueous CB[7] equally well, validating our prior suggestion that they, too, would be ultrahigh affinity CB[7] guests. The present guests, which are based upon either a bicyclo[2.2.2]octane or adamantane core, have no metal atoms, so these results also confirm that the remarkably high affinities of the ferrocene-based guest need not be attributed to metal-specific interactions. Because we used the M2 method to compute the affinities of several of the new host-guest systems prior to synthesizing them, the present results also provide for the first blinded evaluation of this computational method. The blinded calculations agree reasonably well with experiment and successfully reproduce the observation that the new adamantane-based guests achieve extremely high affinities, despite the fact that they position a cationic substituent at only one electronegative portal of the CB[7] host. However, there are also significant deviations from experiment, and these lead to the correction of a procedural error and an instructive evaluation of the sensitivity of the calculations to physically reasonable variations in molecular energy parameters. The new experimental and computational results presented here bear on the physical mechanisms of molecular recognition, the accuracy of the M2 method, and the usefulness of host-guest systems as test-beds for computational methods.
Design, synthesis, radiolabeling, and in vitro and in vivo evaluation of bridgehead iodinated analogues of N -{2-[4-(2-methoxyphenyl)piperazin-1-yl] ethyl}- N -(pyridin-2-yl)cyclohexanecarboxamide (WAY-100635) as potential SPECT ligands for the 5-HT1A receptor
Al Hussainy, Rana,Verbeek, Joost,Van Der Born, Dion,Braker, Anton H.,Leysen, Josée E.,Knol, Remco J.,Booij, Jan,Herscheid
, p. 3480 - 3491 (2011/07/07)
Here we describe the design, synthesis, and pharmacological profile of 5-HT1A receptor ligands related to 1 (WAY-100635). The cyclohexyl moiety in 1 and its O-desmethylated analogue 3 were replaced by the bridgehead iodinated bridge-fused rings: adamantyl, cubyl, bicyclo[2.2.2]octyl, or bicyclo[2.2.1]heptyl. All analogues displayed a (sub)nanomolar affinity for the 5-HT1A receptor in vitro. Compounds 6b and 7b appeared to be selective for this receptor over other relevant receptors and could easily be iodinated with radioactive iodine-123. In humane hepatocytes, [ 123I]6b showed a low propensity for amide hydrolysis and a stable carbon-iodine bond. The biodistribution of [123I]6b and [ 123I]7b in rats revealed that the carbon-iodine bond was also stable in vivo. Unfortunately, the brain uptake and the specificity for both radioligands were significantly lower than those of the parent molecule 1. In conclusion, the designed tracers are not suitable for SPECT imaging.
Unexpectedly similar charge transfer rates through benzo-annulated bicyclo[2.2.2]octanes
Goldsmith, Randall H.,Vura-Weis, Josh,Scott, Amy M.,Borkar, Sachin,Sen, Ayusman,Ratner, Mark A.,Wasielewski, Michael R.
, p. 7659 - 7669 (2008/12/22)
A 4-(pyrrolidin-1-yl)phenyl electron donor and 10-cyanoanthracen-9-yl electron acceptor are attached via alkyne linkages to the bridgehead carbon atoms of bicyclo[2.2.2]octane and all three benzo-annulated bicyclo[2.2.2] octanes. The σ-system of bicyclo[2.2.2]octane provides a scaffold having nearly constant bridge geometry on which to append multiple, weakly interacting benzo π-bridges, so that the effect of incrementally increasing numbers of π-bridges on electron transfer rates can be studied. Surprisingly, photoinduced charge transfer rates measured by transient absorption spectroscopy in toluene show no benefit from increasing the number of bridge π-systems, suggesting dominant transport through the σ-system. Even more surprisingly, the significant changes in hybridization undergone by the σ-system as a result of benzo-annulation also appear to have no effect on the charge transfer rates. Natural Bond Orbital analysis is applied to both σ- and π-communication pathways. The transient absorption spectra obtained in 2-methyltetrahydrofuran (MTHF) show small differences between the benzo-annulated molecules that are attributed to changes in solvation. All charge transfer rates increase significantly upon cooling the MTHF solutions to their glassy state. This behavior is rationalized using combined molecular dynamics/electronic structure trajectories.
EPR and ENDOR Investigations of Dynamic Processes in Sterically Overcrowded Phenoxyl-Type Galvinoxyl Radicals
Gersdorff, J. von,Kirste, B.,Niethammer, D.,Harrer, W.,Kurreck, H.
, p. 416 - 424 (2007/10/02)
The syntheses of tert-butylgalvinol with perdeuteriated tert-butyl groups and 1,4-bicyclooctanebisgalvinol are described.The EPR and ENDOR spectra of the corresponding galvinoxyl monoradicals reveal selective line broadening due to dynamic processes associated with hindered internal rotation of the phenoxy rings.Deuteration of the central tert-butyl group in tert-butylgalvinoxyl gives rise to a substantial decrease of EPR line widths, allowing the determination of the kinetic parameters by means of line-shape analyses (ΔH*=21.8 kJ/mol, ΔS*=-32 J/molK).The biradical 1,4-bicyclooctanebisgalvinoxyl exhibits strong scalar and dipolar electron interactions (D=97 MHz). KEY WORDS EPR ENDOR Galvinoxyls Deuteration Dynamic processes Biradicals.
Synthesis, Characterization, and Chemistry of Bridgehead-Functionalized Bicyclooctanes: Reactions at Neopentyl Sites
Kumar, Kanta,Wang, Shin Shin,Sukenik, Chaim N.
, p. 665 - 670 (2007/10/02)
This paper reports the synthesis and characterization of a series of 15 new, symmetric, 1,4-disubstituted bicyclooctyl derivatives.Beyond detailing their syntheses and spectral properties, it describes the scope of synthetic transformations that ca
Mild Conversion of Carboxamides and Carboxylic Acid Hydrazides to Acids and Esters
Greenlee, William J.,Thorsett, Eugene D.
, p. 5351 - 5353 (2007/10/02)
A mild and selective conversion of unsubstituted carboxamides and carboxylic acid hydrazides to the corresponding acids and esters is brought about by the use of acidic resins.Application of the procedure to several carboxamides and carboxylic acid hydrazides is described.
