Reactivity of biarylazacyclooctynones in copper-free click chemistry

The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry.     

Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality

The study of biomolecules in their native environments is a challenging task because of the vast complexity of cellular systems. Technologies developed in the last few years for the selective modification of biological species in living systems have yielded new insights into cellular processes. Key to these new techniques are bioorthogonal chemical reactions, whose components must react rapidly and selectively with each other under physiological conditions in the presence of the plethora of functionality necessary to sustain life. Herein we describe the bioorthogonal chemical reactions developed to date and how they can be used to study biomolecules.     

A new high-spin isomer in 145Eu

In ¹⁴⁵Eu a high-spin isomer with E _level = 8528 keV and T _1/2 = (3.7 ± 0.4) ns has been observed. The data were obtained by in-beam γ-ray spectroscopy using the reaction ¹²²Sn(²⁷Al,4n)¹⁴⁵Eu at 127 MeV performed at the NORD-BALL spectrometer in Roskilde.     

Lifetimes of triaxial superdeformed states in 163Lu and 164Lu

Lifetimes of states in the yrast superdeformed bands of ¹⁶³Lu and ¹⁶⁴Lu were determined in a Doppler-shift attenuation-method experiment. From fractional Doppler shifts and line shapes, average transition quadrupole moments, Q _t = 8.2_-0.6 ^+1.0 b and 7.1_-0.6 ^+0.5 b, were deduced for one of the bands in ¹⁶³Lu and ¹⁶⁴Lu, respectively. These values are much larger than the quadrupole moment of the normal-deformed yrast band in ¹⁶³Yb, Q _t = 4.9_-0.4 ^+1.3 b, that was also determined in this experiment. Comparison to cranking calculations indicates that both superdeformed bands correspond to a local potential energy minimum with a pronounced triaxiality, γ∼ 20^°. Received: 8 November 2001 / Accepted: 9 January 2002     

Comparative quadrupole moments of triaxial superdeformed states in 163, 164, 165Lu

Average transition quadrupole moments in the yrast triaxial superdeformed bands of ¹⁶³Lu, ¹⁶⁴Lu and ¹⁶⁵Lu were determined in a Doppler-shift attenuation-method experiment. Fractional Doppler shifts were determined in γ-ray coincidence spectra measured with the Gammasphere array. The transition quadrupole moments derived from these data show a decrease from ¹⁶³Lu to ¹⁶⁵Lu which is not predicted by total-energy surface calculations. Received: 12 August 2002 / Accepted: 23 October 2002 / Published online: 10 December 2002 RID="a" ID="a"e-mail: schoenwa@iskp.uni-bonn.de Communicated by D. Schwalm     

A rotational band in82Zr

The neutron deficient nucleus⁸²Zr has been studied through the reaction⁵⁸Ni(²⁸Si, 2p 2n)⁸²Zr with a calculated cross section of 0.3% of the total fusion cross section atE(²⁸Si)=128 MeV. Gamma rays from excited states of⁸²Zr were measured and identified using the NORDBALL escape-suppression array at the Niels Bohr Institute. Reaction channel selection was performed by use of neutron and charged particle detector arrays in conjunction with the germanium detectors. A rotational band in⁸²Zr has been identified with spins up to 20 ? by analysis of reaction channel selectedγ-γ coincidence matrices. Band crossings were identified at frequencies 0.57 and 0.69 MeV.     

Energy levels of 94Ru observed with the 96Ru(p,t) reaction

The level structure of the neutron-magic nucleus ⁹⁴Ru, up to an excitation energy of 4 MeV, has been studied by means of the (p, t) reaction. Particular emphasis was placed on a search for excited 0⁺ levels, none of which have been reported previously. Among new levels observed in this study are 0⁺ levels at 2.995, 3.615 and 3.770 MeV, and the 3^? octupole vibration at 2.965 MeV.