Synthesis and Properties of Benzo-Fused Indeno[2,1-c]fluorenes.

A set of fully-conjugated indenofluorenes has been synthesized and confirmed by solid-state structure analysis. The indeno[2,1-c]fluorenes and their benzo-fused analogues all contain the antiaromatic as-indacene core. The molecules possess high electron affinities and show a broad absorption that reaches into the near-IR region of the electromagnetic spectrum. All of the featured compounds reversibly accept up to two electrons as revealed by cyclic voltammetry. Analysis of molecule tropicity using NICS-XY scan calculations shows that, while the as-indacene core is less paratropic than s-indacene, benz[a]-annulation further reduces the antiaromaticity of the core. Antiaromatic strength of the as-indacene core can also be tuned by the position of fusion of additional arenes on the outer rings.

Scalable synthesis of 5,11-diethynylated indeno[1,2-b]fluorene-6,12-diones and exploration of their solid state packing.

We report a new synthetic route to 5,11-disubstituted indeno[1,2-b]fluorene-6,12-diones that is amenable to larger scale reactions, allowing for the preparation of gram amounts of material. With this new methodology, we explored the effects on crystal packing morphology for the indeno[1,2-b]fluorene-6,12-diones by varying the substituents on the silylethynyl groups.

Indenofluorenes and derivatives: syntheses and emerging materials applications.

The growing demand for flexible electronic devices and hydrogen storage materials has spurred a resurgence of interest in polyaryl hydrocarbons including graphene, acenes, fullerenes, polythiophenes, etc. Indenofluorenes are another polyaryl molecular scaffold that has shown utility in the organic and hybrid materials arena, with polymers incorporating the indeno[1,2-b]fluorene moiety being common in organic light emitting diodes. This review examines the syntheses and properties of the five distinct indenofluorene regioisomers, with a focus on small molecule applications in organic electronics of this intriguing and somewhat underexplored family of polyaryl hydrocarbons.

Tiagabine in clinical practice: effects on seizure control and behavior.

OBJECTIVE: Preapproval randomized controlled trials of antiepileptic drugs provide data in limited patient groups. We assessed the side effect and seizure reduction profile of tiagabine (TGB) in typical clinical practice. METHODS: Investigators recorded adverse effect (AE), seizure, and assessment-of-benefit data prospectively in sequential patients treated open label with TGB. RESULTS: Two hundred ninety-two patients (39 children) were enrolled to be treated long term with TGB. Seizure types were focal-onset (86%), generalized-onset (12%), both focal- and generalized-onset (0.3%), and multiple associated with Lennox-Gastaut Syndrome (2%). Two hundred thirty-one received at least one dose of TGB (median = 28 mg/day) and had follow-up seizure or AE data reported. Common AEs were fatigue, dizziness, psychomotor slowing, ataxia, gastrointestinal upset, weight change, insomnia, and "others" (mostly behavioral). Serious AEs occurred in 19 patients: behavioral effects (n = 12), status epilepticus (n = 3), others (n = 3), and sudden unexplained death (n = 1). No patients experienced suicidal ideation/behavior, rash, nephrolithiasis, or organ failure. Seizure outcomes were seizure freedom (5%), ≥75% reduction (12%), ≥50% reduction (23%), and increased number of seizures (17%), or new seizure type (1%). CONCLUSIONS: Behavioral AEs occurred in a larger proportion of patients compared to those reported in TGB preapproval randomized controlled trials. A moderate percentage of patients had a meaningful reduction in seizure frequency. In clinical practice, TGB remains a useful antiepileptic drug.

Indeno[2,1-c]fluorene: a new electron-accepting scaffold for organic electronics.

A new class of fully conjugated indenofluorenes has been synthesized and confirmed by solid-state structure analysis. These indeno[2,1-c]fluorene molecules, containing an antiaromatic as-indacene core (in red), possess high electron affinities and show a broad absorption that reaches into the near-IR region of the electromagnetic spectrum. All of the featured compounds reversibly accept up to two electrons. Their electronic properties make this class of compounds attractive for applications in organic electronic devices.

6,12-Diarylindeno[1,2-b]fluorenes: syntheses, photophysics, and ambipolar OFETs.

Herein we report the synthesis and characterization of a series of 6,12-diarylindeno[1,2-b]fluorenes (IFs). Functionalization with electron donor and acceptor groups influences the ability of the IF scaffold to undergo two-electron oxidation and reduction to yield the corresponding 18- and 22-π-electron species, respectively. A single crystal of the pentafluorophenyl-substituted IF can serve as an active layer in an organic field-effect transistor (OFET). The important finding is that the single-crystal OFET yields an ambipolar device that is able to transport holes and electrons.

Synthesis and photophysical properties of expanded dehydrobenzoannulenoannulene trefoils.

A sequential Sonogashira cross-coupling/Pd-mediated oxidative homocoupling strategy affords two-dimensional dehydrobenzoannulene trefoils containing different sizes of the central annulenic ring system. Use of these conditions instead of Cu-mediated homocoupling conditions yields a structural isomer possessing a triphenylene ([6]annulene) core. Noticeable differences in the absorption and emission spectra are observed depending upon the core unit.

Emission from regioisomeric bis(phenylethynyl)benzenes during pulse radiolysis.

Emission from charge recombination between radical cations and anions of a series of regioisomeric 1,4-, 1,3-, and 1,2-bis(phenylethynyl)benzenes (bPEBs) substituted by various electron donor and/or acceptor groups was measured during pulse radiolysis in benzene (Bz). The formation of bPEB in the excited singlet state ((1)bPEB*) can be attributed to the charge recombination between bPEB(*+) and bPEB(*-), which are initially generated from the radiolytic reaction. This mechanism is reasonably explained by the relationship between the annihilation enthalpy change (-DeltaH(o)) for the charge recombination of bPEB(*+) and bPEB(*-) and excitation energy of (1)bPEB*. Since the degree of the pi-conjugation in the S(1) state and HOMO-LUMO levels of bPEB change with the substitution pattern of phenylacetylene groups on the central benzene ring and the various kinds of donor and/or acceptor group, the fine-tuning of the emission color and intensity of bPEB can be easily carried out during pulse radiolysis in Bz. For donor-acceptor-substituted bPEB, it was found that the difference in the charge transfer conjugated pathways between donor and acceptor substituents (linear-, cross-, and "bent"-conjugated pathways) strongly influenced the HOMO-LUMO energy gap.

A past psychiatric history may be a risk factor for topiramate-related psychiatric and cognitive adverse events.

OBJECTIVES: Topiramate (TPM) is a new antiepileptic drug (AED) that has been found to be associated with a high prevalence of cognitive adverse events (CAEs). The prevalence of psychiatric adverse events (PAEs) has yet to be established. The purpose of this study was to determine the prevalence of PAEs related to TPM when used in polytherapy regimens in a large cohort of adult patients with epilepsy, to identify any association between the occurrences of CAEs and PAEs and to identify predictors of PAEs and CAEs. METHODS: Investigators from 16 epilepsy centers (PADS group) prospectively obtained postmarketing safety and efficacy data on 596 patients aged 16 years and older. All data were recorded on standardized data retrieval forms, completed at the initial visit, while follow-up data were obtained every 6 months or at the time of discontinuation. RESULTS: PAEs were identified in 75 (12.6%) patients: 30 (5%) experienced symptoms of depression and 34 (5.7%) of aggressive behavior and irritability, while 9 patients experienced symptoms of psychosis (1.5%). CAEs were reported by 247 (41.5%) patients. There was a significant association between the occurrences of CAEs and PAEs. A past psychiatric history was a predictor of CAEs, while older age and past psychiatric history were predictors of PAEs. CONCLUSIONS: The use of TPM in polytherapy regimens can cause PAEs and CAEs and their occurrence is significantly correlated. Patients with a past psychiatric history may be at a higher risk for experiencing PAEs and CAEs.

Characteristics of patients initiated on the new antiepileptic drugs: a PADS study.

Whereas randomized controlled trials remain a standard for evaluating and comparing efficacy and safety of the new antiepileptic drugs (AEDs), postmarketing drug research offers a useful means of comparing efficacy and safety of new AEDs. However, differences in baseline characteristics of patients in different drug groups create the potential for bias in drug comparison studies. In this study, baseline demographic characteristics of 1,386 patients initiating lamotrigine (LTG), tiagabine (TGB), or topiramate (TPM) were compared to identify patient characteristics that may influence AED use in epilepsy patients. Data were collected at 14 epilepsy centers and included medications, seizure types and syndromes, and prior adverse events. There were 402 patients in the LTG group, 725 TPM, and 259 TGB. The groups differed both in their number of concurrent AEDs (p<0.001) and in their number of prior AEDs (p<0.01). There was no difference in proportion with partial versus generalized epilepsy syndromes. The groups differed in the proportions of patients with complex partial seizures (p=0.049), primary generalized tonic-clonic seizures (p=0.01), and myoclonic seizures (p=0.03). Baseline behavioral adverse event rate was lowest in patients initiating TPM (p<0.01); LTG patients had the lowest rate of prior AED-related rash (p=0.02). There was no relationship between AED assignment and patient age, age of epilepsy onset, epilepsy duration, institutionalization status, gender, or psychiatric history. Numerous epidemiological differences were identified among patients placed on the new AEDs, including current and prior AED profiles, seizure types, and prior adverse event history. Accounting for these differences is of crucial importance because they may bias conclusions of nonrandomized post-marketing trials comparing the drugs.