Elimination reactions of (E)- and (Z)-benzaldehyde O-pivaloyloximes 1 and 2 with DBU in MeCN have been investigated kinetically. The reactions are second order and exhibit substantial values of Hammett rho and k(H)/k(D) values, and an E2 mechanism is evident. The rate of elimination from 2 is approximately 20 000-fold faster than that from 1. For reactions of 1 with DBU in MeCN, a Hammett rho value of 2.4 +/- 0.1, k(H)/k(D) = 2.7 +/- 0.3, DeltaH() = 12.5 +/- 0.2 kcal/mol, and DeltaS() = -31.0 +/- 0.6 eu have been determined. The corresponding values for 2 are rho = 1.4 +/- 0.1, k(H)/k(D) = 7.8 +/- 0.3, DeltaH() = 8.8 +/- 0.1 kcal/mol, and DeltaS() = -23.6 +/- 0.4 eu, respectively. The results indicate that the nitrile-forming anti eliminations from 2 proceed via a more symmetrical transition state with a smaller degree of proton transfer, less negative charge development at the beta-carbon, and greater extent of triple-bond formation than that for the syn elimination.

Background Tendinopathy (pain and tendon degeneration) is associated with repetitive use and mechanical overload. However, the etiology of tendinopathy remains unclear. Clarification of histologic and molecular changes of tendon to repetitive stress could provide better understanding of Achilles tendon disorders related to repetitive stress. Questions/Purposes We asked whether repetitive stress simulating overuse of the Achilles tendon induced (1) histologic changes in rats similar to tendinosis (increased cellularity of fibrocytes, increased disorganization of collagen fiber, and increased roundness of the nucleus of the fibrocyte), (2) increased collagen Type III occurrence, and (3) increased inducible nitric oxide synthase (iNOS) expression. Methods We used an exercise protocol simulating repetitive, jerky, eccentric contraction of the triceps surae in 15 rats. We conducted the exercise for 2 hours per day, three times per week using the right rear legs only and the left legs as internal controls. We harvested Achilles tendons after either 2, 4, or 6 weeks of exercise, and evaluated changes in tendon thickness, fibrocyte count, collagen fiber arrangement, collagen fiber type, and occurrence of iNOS. Results Exercised Achilles tendons showed increased cellularity of fibrocytes at 4 and 6 weeks of exercise, and disorganized collagen fiber arrangement at 6 weeks of exercise. There was a trend for Type III collagen occurrence being greater in experimental groups. Expression of iNOS increased after 2 and 4 weeks of exercise when compared with that of the controls, but decreased after 6 weeks. Conclusions These observations suggest repetitive, synchronized, passive, and jerky exercise induced by electrical stimulation can lead to the tendinosis-like changes in the Achilles tendons in rats with imbalance between synthesis and degeneration after 4 weeks of exercise. Clinical Relevance This newly designed exercise protocol may be used to design an animal model of Achilles tendon overuse. With this model, therapeutic interventions of tendinopathy could be analyzed by investigation of tendon biology and response in terms of histologic and molecular changes.

Elimination reactions of (E)-and (Z)-benzaldehyde O-benzoyloximes 1 and 2 with DBU in MeCN have been investigated kinetically. The reactions are second order and exhibit substantial values of Hammett F and k H /k D values, and an E2 mechanism is evident. The rate of elimination from 2 is approximately 36000 fold faster than that from 1. For reactions of 1 with DBU in MeCN, k H /k D ) 3.3 ( 0.2, Hammett F value of 2.19 ( 0.05, β 1g ) -0.49 ( 0.02, ∆H q ) 10.4 ( 0.6 kcal/mol, and ∆S q ) -34.3 ( 2.6 eu have been determined. The corresponding values for 2 are k H /k D ) 7.3 ( 0.2, F ) 1.21 ( 0.05, β 1g ) -0.40 ( 0.01, ∆H q ) 6.8 ( 0.5 kcal/mol, and ∆S q ) -25.8 ( 1.9 eu, respectively. The results indicate that the anti-eliminations from 2 proceed via more symmetrical transition states with smaller degrees of proton transfer and N R -OC(O)Ar bond cleavage, less negative charge development at the β-carbon, and a greater extent of triple bond formation than that for the syn-elimination.

We were unable to identify differences between the types of insoles in terms of their clinical effects or between anatomical locations of foot lesions in the two groups, but both groups improved. Therapeutic shoes plus soft insoles might be effective enough in terms of foot pain and foot function for specific patients with rheumatoid foot problems regardless of the location of foot pathology.

Elimination reactions of (Z)-thiophene- and (Z)-furan-2-carbaldehyde O-benzoyloximes 1 and 2 with DBU in MeCN have been investigated kinetically. The reactions are second order and exhibit substantial values of Hammett ρ and k H/k D values, and an E2 mechanism is evident. The relative rates of elimination from (Z)-ArCHNOC(O)C6H4Y are 1/1.1/0.6 for Ar = phenyl/thienyl/furyl, respectively. For reactions of 1 with DBU in MeCN, k H/k D = 8.2 ± 0.1, Hammett ρ = 1.22 ± 0.19, β1g = −0.43 ± 0.01, ΔH ⧧ = 5.9 ± 0.1 kcal/mol, and ΔS ⧧ = −28.5 ± 0.3 eu have been determined. The corresponding values for 2 are k H/k D = 8.8 ± 0.2, ρ = 1.87 ± 0.05, β1g = −0.55 ± 0.10, ΔH ⧧ = 6.5 ± 0.1 kcal/mol, and ΔS ⧧ = −29.0 ± 1.5 eu. The k H/k D, Hammett ρ, and |β1g| values increase as the β-aryl group is changed in the order phenyl < thienyl < furyl. The results indicate that the transition state structure for the nitrile-forming elimination changes slightly toward product-like with the change of the β-aryl group.

Reactions of the ( E ) -0-arylbenzaldehyde oximes (1; Ar = 2,4-dinitrophenyl), (2; Ar = p-nitrophenyl), and (3; Ar = phenyl) with O Hin 60% aq. DMSO have been investigated. The eliminations are quantitative, producing only benzonitriles and aryloxides. The observation of second-order kinetics, k20D-/kZOH-= 1 .I 5-1.84, and PI, = -0.59 is consistent with an €2 mechanism. The Hammett p and k Z O D -/ k z O H -values increased with poorer leaving groups. For a given substrate the k 2 0 D -/ k z O H -value remained (within experimental error) roughly constant, in spite of changes in the P-aryl substituents. These changes in transition state parameters can be interpreted in terms of the differing nitrile-forming transition states involved.

This case report demonstrates that combination of ultrasonography with electrophysiological studies can provide more detailed information about the changes of nerve structures and lesion sites.

Elimination reactions of (E)-2,4-dinitrobenzaldehyde O-aryloximes 1−3 promoted by EtO-, PhC(CH3)NO-/PhC(CH3)NOH, and CF3CH2O-/CF3CH2OH buffers in ethanol have been studied kinetically. The reactions produced 2,4-dinitrobenzonitrile and aryloxides as the only products. The observed second-order kinetics, Brønsted β = 0.55−0.75, |βlg| = 0.39−0.48 are consistent with the E2 mechanism. The Brønsted β decreased as the leaving group was made more nucleofugic and the |βlg| increased with a weaker base. The result can be described by a positive interaction coefficient, pxy = ∂β/∂pK 1g = ∂β1g/∂pK BH > 0, which provides additional support for the E2 mechanism.