Stereoelectronic and Resonance Effects on the Rate of Ring Opening of N-Cyclopropyl-Based Single Electron Transfer Probes.

N-Cyclopropyl-N-methylaniline (5) is a poor probe for single electron transfer (SET) because the corresponding radical cation undergoes cyclopropane ring opening with a rate constant of only 4.1 × 104 s-1, too slow to compete with other processes such as radical cation deprotonation. The sluggish rate of ring opening can be attributed to either (i) a resonance effect in which the spin and charge of the radical cation in the ring-closed form is delocalized into the phenyl ring, and/or (ii) the lowest energy conformation of the SET product (5•+) does not meet the stereoelectronic requirements for cyclopropane ring opening. To resolve this issue, a new series of N-cyclopropylanilines were designed to lock the cyclopropyl group into the required bisected conformation for ring opening. The results reveal that the rate constant for ring opening of radical cations derived from 1'-methyl-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-quinoline] (6) and 6'-chloro-1'-methyl-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-quinoline] (7) are 3.5 × 102 s-1 and 4.1 × 102 s-1, effectively ruling out the stereoelectronic argument. In contrast, the radical cation derived from 4-chloro-N-methyl-N-(2-phenylcyclopropyl)aniline (8) undergoes cyclopropane ring opening with a rate constant of 1.7 × 108 s-1, demonstrating that loss of the resonance energy associated with the ring-closed form of these N-cyclopropylanilines can be amply compensated by incorporation of a radical-stabilizing phenyl substituent on the cyclopropyl group. Product studies were performed, including a unique application of EC-ESI/MS (Electrochemistry/ElectroSpray Ionization Mass Spectrometry) in the presence of 18O2 and H218O to elucidate the mechanism of ring opening of 7•+ and trapping of the resulting distonic radical cation.

Does Metal Ion Complexation Make Radical Clocks Run Fast? An Experimental Perspective.

The rate constant for the ß-scission of the cumyloxyl radical (kß) was measured in the presence of various added electrolytes in acetonitrile and DMSO solvent. The results show that in CH3CN, kß increases in the presence of added electrolyte, roughly paralleling the size of the cation: Li+ > Mg2+ ≈ Na+ > nBu4N+ > no added electrolyte. As suggested by Bietti et al. earlier, this effect is attributable to stabilizing ion-dipole interactions in the transition state of the developing carbonyl group, a conclusion further amplified by MO calculations (gas phase) reported herein. Compared to the gas phase predictions, however, this effect is seriously attenuated in solution because complexation of the cation to the electrophilic alkoxyl radical (relative to the solvent, CH3CN) is very weak. Because the interaction of Li+ and Na+ is much stronger with DMSO than with CH3CN, addition of these ions has no effect on the rate of ß-scission.

Interplay between Structure and Mechanism in Reductive Dissociative Electron Transfers to α,ß -Epoxyketones.

The electrochemical reduction of several α,ß -epoxyketones was studied using cyclic (linear sweep) voltammetry, convolution voltammetry, and homogeneous redox catalysis. The results were reconciled to pertinent theories of electron transfer. α,ß -Epoxyketones undergo dissociative electron-transfer reactions with C-O bond cleavage, via both stepwise and concerted mechanisms, depending on their structure. For aliphatic ketones, the preferred mechanism of reduction is consistent with the "sticky" concerted model for dissociative electron transfer. Bond cleavage occurs simultaneously with electron transfer, and there is a residual, electrostatic interaction in the ring-opened (distonic) radical anion. In contrast, for aromatic ketones, because the ring-closed radical anions are resonance-stabilized and exist at energy minima, a stepwise mechanism operates (electron transfer and bond cleavage occur in discrete steps). The rate constants for ring opening are on the order of 108  s-1 , and not significantly affected by substituents on the 3-membered ring (consistent with C-O bond cleavage). These results and conclusions were fully supported and augmented by molecular orbital calculations.

Chin region: management of grooves and mandibular hypoplasia with alloplastic implants.

Using just a small number of alloplastic extended mandibular implants can fulfill more than 95% of the needs of the facial plastic surgeon in chin and prejowl augmentation to restore balance to a patient's jawline. Current chin implants are artistically designed to impart good form and fit and give significant improvement for a somewhat uncomplicated procedure.

A survey of hallucinogenic mushroom use, factors related to usage, and perceptions of use among college students.

BACKGROUND: Recreational usage and attitudes toward psilocybin-containing hallucinogenic mushrooms among college students are seldom explored. METHODS: We surveyed 882 randomly selected undergraduates at Skidmore College in upstate New York and quantified whether participants had ever used psilocybin mushrooms, their attitudes toward the drug, and polydrug use. RESULTS: There were 409 responses and 29.5% of the sample reported psilocybin use. Among users, the mean number of times they reported using mushrooms was 3.4 (mode=1). The top factors cited that influenced their decisions to try hallucinogenic mushrooms for the first time were 'curiosity', 'to achieve a mystical experience', and 'introspection'. Users and non-users had significantly different perceptions of mushrooms: non-users were more likely to say that hallucinogenic mushrooms were addictive and had the potential for abuse than users. Users did not believe that psilocybin negatively impacts their academics, mental health, or physical health, while non-users did. Both users and non-users of psilocybin reported high life-time use of alcohol (97% vs 96%, respectively), marijuana (98% vs 73%, respectively) and tobacco (82% vs 54%, respectively). Psilocybin users were significantly more likely to use other drugs such as cocaine, ecstasy, opiates, non-prescribed prescription drugs, opiates, and lysergic acid diethylamide (LSD) than non-users of psilocybin. CONCLUSION: This study uncovers important insights into hallucinogenic mushroom use by college students.

Lateral sinus thrombosis: a review of seven cases and proposal of a management algorithm.

OBJECTIVE: To evaluate the demographics, diagnosis, management, and outcomes of lateral sinus thrombosis in a pediatric population, and to propose a new treatment algorithm. METHODS: Retrospective review of seven patients. RESULTS: Patients averaged 7.4 years of age. They commonly presented with headache and otalgia (seven of seven patients), and nausea and vomiting (six of seven patients). All patients had abnormal otoscopy, and four of seven patients had a lateral rectus palsy, but fever was not always present (only three of seven patients). All patients underwent MRI with venography (MRV) for diagnosis. All patients were admitted to the hospital (average length of stay 8 days) and treated with antibiotics (six of seven patients with i.v. ceftriaxone). Five of seven were treated with simple mastoidectomy and concurrent middle ear ventilation tubes; two patients received only medical treatment. The average follow up was 114 months (range 33-387 months). Two patients had long-term sequela: one had persistent mild lateral gaze diplopia and another had unilateral moderate to severe high frequency sensorineural hearing loss. Six of seven patients had follow up imaging (average 15 months, range 1-40 months). Four of six patients showed recanalization of the lateral sinus on repeat imaging. Based on the current experience in the modern era of MRV and broad-spectrum antibiotics, a new treatment algorithm is proposed. CONCLUSIONS: Lateral sinus thrombosis is an uncommon cranial complication of otitis media. The advent of non-invasive diagnosis and effective broad-spectrum antibiotics has drastically decreased the mortality and altered the diagnostic and treatment paradigm.

Cyclopropyl conjugation and ketyl anions: when do things begin to fall apart?

Results pertaining to the electrochemical reduction of 1,2-diacetylcyclopropane (5), 1-acetyl-2-phenylcyclopropane (6), 1-acetyl-2-benzoylcyclopropane (7), and 1,2-dibenzoylcyclopropane (8) are reported. While 6*- exists as a discrete species, the barrier to ring opening is very small (<1 kcal/mol) and the rate constant for ring opening is >10(7) s(-1). For 7 and 8, the additional resonance stabilization afforded by the benzoyl moieties results in significantly lower rate constants for ring opening, on the order of 10(5)-10(6) s(-1). Electron transfer to 8 serves to initiate an unexpected vinylcyclopropane --> cyclopentene type rearrangement, which occurs via a radical ion chain mechanism. The results for reduction of 5 are less clear-cut: The experimental results suggest that the reduction is unexceptional, with a symmetry coefficient alpha