Photocatalytic Dearomative Intermolecular [2 + 2] Cycloaddition of Heterocycles for Building Molecular Complexity.

Indole and indoline rings are important pharmacophoric scaffolds found in marketed drugs, agrochemicals, and biologically active molecules. The [2 + 2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp3-rich cyclobutane-fused scaffolds with potential applications in drug discovery programs. A general platform for visible-light mediated intermolecular [2 + 2] cycloaddition of indoles with alkenes has been realized. A substrate-based screening approach led to the discovery of tert-butyloxycarbonyl (Boc)-protected indole-2-carboxyesters as suitable motifs for the intermolecular [2 + 2] cycloaddition reaction. Significantly, the reaction proceeds in good yield with a wide variety of both activated and unactivated alkenes, including those containing free amines and alcohols, and the transformation exhibits excellent regio- and diastereoselectivity. Moreover, the scope of the indole substrate is very broad, extending to previously unexplored azaindole heterocycles that collectively afford fused cyclobutane containing scaffolds that offer unique properties with functional handles and vectors suitable for further derivatization. DFT computational studies provide insights into the mechanism of this [2 + 2] cycloaddition, which is initiated by a triplet-triplet energy transfer process. The photocatalytic reaction was successfully performed on a 100 g scale to provide the dihydroindole analog.

Change in Incidence and Epidemiology of Inflammatory Bowel Disease in 2- to 9-Year-olds in Southwest England.

OBJECTIVES: The aim of the study was to characterize epidemiology, phenotype, and clinical outcome of Inflammatory Bowel Disease (IBD) diagnosed ages 2 to 9 years, and compare age groups 2 to 5 and 6 to 9 years. METHODS: A population-based retrospective cohort study of all <10-year-olds diagnosed with IBD between 2004 and 2017 in Southwest England was performed. Patients were divided into age groups at diagnosis. Demographics, investigations, and phenotype at diagnosis were collected. Treatments and outcomes were analysed at 1, 2, 5, and 10 years follow-up. Poisson regression was used for IBD incidence rate ratios; Wald test for variation by age group; parametric/nonparametric tests for phenotype. RESULTS: There were 666 new paediatric IBD (pIBD) patients ages ≤16 years, from which 136 were 2 to 9 (2-5 years: 32; 6-9 years: 104). Incidence of pIBD increased from 4 to 6 cases per 100,000 whereas in A1a group was stable around 2 cases per 100,000. Crohn Disease (CD) children were majority boys, 2- to 5-year-olds were more likely to have ileal sparing than 6 to 9-year group but had similar rates of surgery and anti-TNF therapy. Two- to 5-year-olds with ulcerative colitis were more likely to have surgery but rates for anti-TNF therapy were similar. Sixteen percent of 2- to 5-year-olds and 10% of 6- to 9-year-olds had IBD-unclassified. No significant differences in symptoms or time to diagnosis were found. CONCLUSIONS: Twenty percent of pIBD in Southwest England are 2 to 9 years old. pIBD incidence has increased but is stable in that group. In terms of phenotypic differences, ileal sparing in CD and pancolitis and surgery in UC, are more likely in 2- to 5-year-olds.

Diagnosis of celiac disease is being missed in over 80% of children particularly in those from socioeconomically deprived backgrounds.

Population-based screening studies have documented prevalence of celiac disease (CD) at 1% at age 7 years, but 90% of children remain undiagnosed. This prospective cohort study aims to examine whether observed differences in diagnosis rates of CD exist between children from different socioeconomic groups and how this has changed over a 12-year period. All children aged ≤15 years with a postcode within South West of England (SWE) diagnosed with CD during a 12-year period (1999-2010) when all diagnoses were based on endoscopic histology were included in the study. The incidence rates in socioeconomic groups were determined using the Index of Multiple Deprivation Score and Office of National Statistics population data. Four hundred fifteen children were diagnosed with CD; 65 within the City of Bristol (CoB). Diagnosis rate rose 4.2 times in SWE and 3.1 times in CoB between the first and last 4 years of the study. The rate was 1.6 times higher in the least socioeconomically deprived compared to most deprived (2.2 times in CoB), and the gap widened over the 12 years. Missed cases estimates for CoB and SWE are at least 83% and 91%, respectively.Conclusion: These findings suggest that while incidence of diagnosed CD in children has increased over a 12-year period, 83-91% remained undiagnosed. Socioeconomically deprived children are more likely to be underdiagnosed, and the gap between the least and most deprived has widened. To fully address massive underdiagnosis, further strategies including pilot studies using finger prick serological mass screening for CD in children entering primary schools are needed. What is Known: • Epidemiological studies record a 1% prevalence of celiac disease (CD), but up to 90% of children may remain undiagnosed. • Previous studies have documented an increased incidence of CD in higher socioeconomic groups, but proposed reasons remain conflicting. What is New: • Incidence of diagnosed CDhas gone up across all social classes but more so in higher socioeconomic groups and there is an increasing health/wealth gap. • This study estimates that 83-91% of children with CD are still being missed despite improved and easily available serological testing and suggest that population screening should be reconsidered.

Acute Gastroenteritis in Children of the World: What Needs to Be Done?

The incidence of gastroenteritis has greatly reduced due to improved hygiene conditions in developing countries and the use of rotavirus vaccine. Still thousands of children, however, die from gastroenteritis, most of them in poor countries. Yet gastroenteritis management is simple, inexpensive, and effective and is largely the same all over the world. Universal guidelines for gastroenteritis guide the management and include simple interventions put forward early in the course of the disease. Treatment includes rehydration, continuing oral feeding, and anti-infective drugs in selected clinical conditions related to the symptoms or to host-related risk, and possible additional drug treatment to reduce the duration and severity of symptoms. There may be minor geographical differences in the treatment applied due to health care organizations that do not substantially change the standard universal recommendations. Prevention is recommended with sanitation interventions and rotavirus universal immunization. Implementation of those interventions through educational initiatives and local programs in target areas are needed. A series of recommendations for interventions, education, and research priorities are included here with the aim of reducing the burden of gastroenteritis, to be pursued by scientists, physicians, policy makers, and stakeholders involved. They include the need of recommendations for the management of gastroenteritis in malnourished children, in those with chronic conditions, in neonates, and in emergency settings. A reference system to score dehydration, the definition of optimal composition of rehydration solution and the indications for anti-infective therapy are also included. Rotavirus immunization should be actively promoted, and evidence-based guidelines should be universally implemented. Research priorities are also indicated.

Evidence Supporting Serology-based Pathway for Diagnosing Celiac Disease in Asymptomatic Children From High-risk Groups.

OBJECTIVE: The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing celiac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titer of >10 times upper limit of normal (>10× ULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. The aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups. METHODS: From March 2007 to February 2017, prospective data on anti-tTG titer, age, sex, and reason for screening were collected at diagnostic endoscopy on all asymptomatic children being diagnosed as having CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titers was analyzed. RESULTS: A total of 157 asymptomatic children were diagnosed as having CD. Eighty-four of 157 (53.5%) had antitTG >10× ULN (normal <10 IU/mL) and 75 of 84 were from high-risk groups. All 75 had definitive histological evidence (Marsh-Oberhuber 3a-3c) of small bowel enteropathy. Fifty-three of 84 children had anti-tTG >200 IU/mL and total villous atrophy was present in 29 of 53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around £1275 per child in the United Kingdom. CONCLUSIONS: All 75 asymptomatic children from high-risk groups with anti-tTG >10× ULN had histology-proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children.

Universal Recommendations for the Management of Acute Diarrhea in Nonmalnourished Children.

OBJECTIVE: Despite a substantial consistency in recommendations for the management of children with acute gastroenteritis (AGE), a high variability in clinical practice and a high rate of inappropriate medical interventions persist in both developing and developed countries.The aim of this study was to develop a set of clinical recommendations for the management of nonseverely malnourished children with AGE to be applied worldwide. METHODS: The Federation of International Societies of Pediatric Gastroenterology, Hepatology, and Nutrition (FISPGHAN) Working Group (WG) selected care protocols on the management of acute diarrhea in infants and children aged between 1 month and 18 years. The WG used a 3-step approach consisting of: systematic review and comparison of published guidelines, agreement on draft recommendations using Delphi methodology, and external peer-review and validation of recommendations. RESULTS: A core of recommendations including definition, diagnosis, nutritional management, and active treatment of AGE was developed with an overall agreement of 91% (range 80%-96%). A total of 28 world experts in pediatric gastroenterology and emergency medicine successively validated the set of 23 recommendations with an agreement of 87% (range 83%-95%). Recommendations on the use of antidiarrheal drugs and antiemetics received the lowest level of agreement and need to be tailored at local level. Oral rehydration and probiotics were the only treatments recommended. CONCLUSIONS: Universal recommendations to assist health care practitioners in managing children with AGE may improve practitioners' compliance with guidelines, reduce inappropriate interventions, and significantly impact clinical outcome and health care-associated costs.

Investigation of the combined effect of MgO and PEG on the release profile of mefenamic acid prepared via hot-melt extrusion techniques.

This study aimed to investigate the combined effect of magnesium oxide (MgO) as an alkalizer and polyethylene glycol (PEG) as a plasticizer and wetting agent in the presence of Kollidon® 12 PF and 17 PF polymer carriers on the release profile of mefenamic acid (MA), which was prepared via hot-melt extrusion technique. Various drug loads of MA and various ratios of the polymers, PEG 3350 and MgO were blended using a V-shell blender and extruded using a twin-screw extruder (16-mm Prism EuroLab, ThermoFisher Scientific, Carlsbad, CA) at different screw speeds and temperatures to prepare a solid dispersion system. Differential scanning calorimetry and X-ray diffraction data of the extruded material confirmed that the drug existed in the amorphous form, as evidenced by the absence of corresponding peaks. MgO and PEG altered the micro-environmental pH to be more alkaline (pH 9) and increased the hydrophilicity and dispersibility of the extrudates to enhance MA solubility and release, respectively. The in vitro release study demonstrated an immediate release for 2 h with more than 80% drug release within 45 min in matrices containing MgO and PEG in combination with polyvinylpyrrolidone when compared to the binary mixture, physical mixture and pure drug.

Limited role of HLA DQ2/8 genotyping in diagnosing coeliac disease.

The European guidelines for diagnosing coeliac disease in children were revised in 2012. These recommend that in symptomatic children, a diagnosis of coeliac disease can be made without small-bowel biopsies provided their anti-tissue transglutaminase (anti-tTG) titre is >10 times of upper-limit-of-normal (>10×ULN) and anti-endomysial antibody is positive. In order to firm up the diagnosis in these children with very high anti-tTG titre, HLA-DQ2/DQ8 should be checked and be positive. Approximately 25-40% of white Caucasian population has HLA-DQ2/DQ8 haplotype. However, only 0.1-1% of the population will develop coeliac disease. Therefore, HLA-DQ2/DQ8 testing must not be done to 'screen' or 'diagnose' children with coeliac disease. Its use by paediatricians should be limited to children with anti-tTG>10×ULN, where the diagnosis of coeliac disease is being made on serology alone. A review of case referrals made to a tertiary paediatric gastroenterology centre in Southwest England demonstrated that HLA-DQ2/DQ8 testing is being requested inappropriately both in primary and secondary care suggesting a poor understanding of its role in diagnosis of coeliac disease. This article aims to clarify the role of HLA-DQ2/DQ8 testing for clinicians working in non-specialist settings.

Comparison of Recommendations in Clinical Practice Guidelines for Acute Gastroenteritis in Children.

OBJECTIVE: Acute gastroenteritis (AGE) is a major cause of child mortality and morbidity. This study aimed at systematically reviewing clinical practice guidelines (CPGs) on AGE to compare recommendations and provide the basis for developing single universal guidelines. METHODS: CPGs were identified by searching MEDLINE, Cochrane-Library, National Guideline Clearinghouse and Web sites of relevant societies/organizations producing and/or endorsing CPGs. RESULTS: The definition of AGE varies among the 15 CPGs identified. The parameters most frequently recommended to assess dehydration are skin turgor and sunken eyes (11/15, 73.3%), general appearance (11/15, 66.6%), capillary refill time, and mucous membranes appearance (9/15, 60%). Oral rehydration solution is universally recognized as first-line treatment. The majority of CPGs recommend hypo-osmolar (Na 45-60 mmol/L, 11/15, 66.6 %) or low-osmolality (Na 75 mmol/L, 9/15, 60%) solutions. In children who fail oral rehydration, most CPGs suggest intravenous rehydration (66.6%). However, nasogastric tube insertion for fluid administration is preferred according by 5/15 CPGs (33.3%). Changes in diet and withdrawal of food are discouraged by all CPGs, and early refeeding is strongly recommended in 13 of 15 (86.7%). Zinc is recommended as an adjunct to ORS by 10 of 15 (66.6%) CPGs, most of them from low-income countries. Probiotics are considered by 9 of 15 (60%) CPGs, 5 from high-income countries. Antiemetics are not recommended in 9 of 15 (60%) CPGs. Routine use of antibiotics is discouraged. CONCLUSIONS: Key recommendations for the management of AGE in children are similar in CPGs. Together with accurate review of evidence-base this may represent a starting point for developing universal recommendations for the management of children with AGE worldwide.

Supramolecular synthesis based on piperidone derivatives and pharmaceutically acceptable co-formers.

The target complexes, bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} butanedioate, 2C27H36N3O(+)·C4H4O4(2-), (II), and bis{(E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-oxopiperidinium} decanedioate, 2C27H36N3O(+)·C10H16O4(2-), (III), were obtained by solvent-mediated crystallization of the active pharmaceutical ingredient (API) (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone and pharmaceutically acceptable dicarboxylic (succinic and sebacic) acids from ethanol solution. They have been characterized by melting point, IR spectroscopy and single-crystal X-ray diffraction. For the sake of comparison, the structure of the starting API, (E,E)-3,5-bis[4-(diethylamino)benzylidene]-4-piperidone methanol monosolvate, C27H35N3O·CH4O, (I), has also been studied. Compounds (II) and (III) represent salts containing H-shaped centrosymmetric hydrogen-bonded synthons, which are built from two parallel piperidinium cations and a bridging dicarboxylate dianion. In both (II) and (III), the dicarboxylate dianion resides on an inversion centre. The two cations and dianion within the H-shaped synthon are linked by two strong intermolecular N(+)-H···(-)OOC hydrogen bonds. The crystal structure of (II) includes two crystallographically independent formula units, A and B. The cation geometries of units A and B are different. The main N-C6H4-C=C-C(=O)-C=C-C6H4-N backbone of cation A has a C-shaped conformation, while that of cation B adopts an S-shaped conformation. The same main backbone of the cation in (III) is practically planar. In the crystal structures of both (II) and (III), intermolecular N(+)-H···O=C hydrogen bonds between different H-shaped synthons further consolidate the crystal packing, forming columns in the [100] and [101] directions, respectively. Salts (II) and (III) possess increased aqueous solubility compared with the original API and thus enhance the bioavailability of the API.

Pyridine-4-carbaldehyde-fumaric acid (2/1).

In the title co-crystal, 2C6H5NO·C4H4O4, two crystallographically different hydrogen-bonded trimers are formed, one in which the components occupy general positions, and one generated by an inversion centre. This results in the uncommon situation of Z = 3 for a triclinic crystal. In the formula units, mol-ecules are linked by O-H⋯N hydrogen bonds.

3,4-Di-amino-pyridinium hydrogen malonate.

In the title salt, C5H8N3 (+)·C3H3O4 (-), the 3,4-di-amino-pyridinium cation is almost planar, with an r.m.s. deviation of 0.02 Å. The conformation of the hydrogen malonate anion is stabilized by an intra-molecular O-H⋯O hydrogen bond, which generates an S(6) ring. In the crystal, N-H⋯O hydrogen bonds link cations and anions into layers parallel to the ab plane.

Pyrimidine-2,4-diamine acetone monosolvate.

In the title compound, C(4)H(6)N(4)·C(3)H(6)O, the pyrimidine-2,4-diamine mol-ecule is nearly planar (r.m.s. deviation = 0.005 Å), with the endocyclic angles covering the range 114.36 (10)-126.31 (10)°. In the crystal, N-H⋯N and N-H⋯O hydrogen bonds link the mol-ecules into ribbons along [101], and weak C-H⋯π inter-actions consolidate further the crystal packing.

Faecal prevalence and histopathological evaluation of coccidiosis in bovine calves.

Bovine coccidiois, caused by Eimeria spp. is widely prevalent around the globe and responsible for huge economic losses by causing morbidity and mortality among young calves. The present study was designed to evaluate the prevalence as well as to evaluate histopathological alterations associated with it. The faecal samples were collected from 700 bovine calves upto two month of age from August 2019 to July 2021 and screened for Eimeria oocycts. The intestinal tissue samples of 37 calves were also collected which died during the study period after showing symptoms of diarrhea and examined for histological lesions. The faecal prevalence of Eimeria observed in our study was 2.29% (16/700) while in tissue samples only two out of 37 were found positive for Eimeria infection. Tissue sections revealed various stages of Eimeria gametogony, variable congestion, haemorrhage, and necrosis along with cryptic dilatation and mononuclear cell infiltration. Coccidia was not found to be associated with season, age and sex of calf. Bovine coccidiosis was found to be endemic with low prevalence but severe onset characterized by moderate to severe congestion and inflammatory reaction mainly in the ileum and caecum.

Diagnostic workup of paediatric patients with inflammatory bowel disease in Europe: results of a 5-year audit of the EUROKIDS registry.

OBJECTIVE: In 2005, the Inflammatory Bowel Disease (IBD) Working Group of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition published consensus guidelines on the diagnostic workup of paediatric IBD, the Porto criteria. According to these guidelines, children suspected of having IBD should undergo an oesophagogastroduodenoscopy (OGD), ileocolonoscopy, and (except in cases of definitive ulcerative colitis) adequate imaging of the small bowel. To audit and evaluate the diagnostic workup of paediatric patients with IBD in Europe, the Working Group created EUROKIDS, a prospective, Web-based registry of newly diagnosed paediatric patients with IBD. METHODS: Patients with IBD (ages 0-18 years) were registered in 44 centres in 18 countries. Data on diagnostic workup were analysed according to the year of diagnosis, type of IBD, and centre size. Diagnostic yield of OGD and ileal intubation were evaluated. RESULTS: Between 2004 and 2009, 2087 newly diagnosed patients were correctly registered. Both OGD and ileocolonoscopy had been performed in 64% of all of the patients and increased significantly from year 1 (52 %) to 5 (71%, P  <  0.001). Small-bowel follow-through use decreased during the years (year 1 n = 213, year 5 n = 108; P < 0.001), whereas magnetic resonance imaging use increased (year 1 n  = 25, year 5 n  = 171; P < 0.001). Patients diagnosed as having Crohn disease (CD, 59%) and ulcerative colitis (58%) were more likely to have had a complete diagnostic workup than patients diagnosed as having IBD unclassified (45%). In CD, the diagnostic yield of OGD was 7.5% and the yield of ileal intubation was 13%. CONCLUSIONS: The quality of diagnostic workup in paediatric patients with IBD increased steadily between 2004 and 2009. Small-bowel imaging by magnetic resonance imaging superseded the use of small-bowel follow-through. OGD and ileal intubation contributed to a definitive diagnosis of CD.

6-Methyl-pyridin-2-amine.

In the title mol-ecule, C6H8N2, the endocyclic angles are in the range 118.43 (9)-122.65 (10)°. The mol-ecular skeleton is planar (r.m.s. deviation = 0.007 Å). One of the two amino H atoms is involved in an N-H⋯N hydrogen bond, forming an inversion dimer, while the other amino H atom participates in N-H⋯π inter-actions between the dimers, forming layers parallel to (100).

Evidence supporting safe diagnosis of coeliac disease in children with antitissue transglutaminase titre ≥5 times upper limit of normal.

OBJECTIVE: European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD. METHODS: Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant). RESULTS: 722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used. CONCLUSION: 99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.

Structural and Thermal Characterization of Halogenated Azidopyridines: Under-Reported Synthons for Medicinal Chemistry.

Owing to their participation in Click reactions, bifunctional azides are valuable intermediates in the preparation of medicines and biochemical tool compounds. Despite the privileged nature of pyridines among pharmaceutical scaffolds, reports of the synthesis and characterization of azidopyridines bearing a halogen substituent for further elaboration are almost completely unknown in the literature. As azidopyridines carry nearly equal numbers of nitrogen and carbon atoms, we hypothesized that safety concerns limited the application of these useful bifunctional building blocks in medicinal and biological chemistry. To address this concern, we prepared and characterized nine azidopyridines bearing a single fluorine, chlorine, or bromine atom. All were examined by differential scanning calorimetry (DSC), in which they demonstrated exotherms of 228-326 kJ/mol and onset temperatures between 119 and 135 °C. Selected azidopyridines were advanced to mechanical stress testing, in which impact sensitivity was noted for one regioisomer of C5H3FN4. The utility of these versatile intermediates was demonstrated through their use in a variety of Click reactions and the diversification of the halogen handles.

Kinetic and Thermodynamic Considerations in the Rh-Catalyzed Enantioselective Hydrogenation of 2-Pyridyl-Substituted Alkenes.

The mechanism of asymmetric hydrogenation of 2-pyridyl alkenes catalyzed by chiral Rh-phosphine complexes at ambient temperature is examined using kinetic, spectroscopic, and computational tools. The reaction proceeds with reversible substrate binding followed by rate-determining addition of hydrogen. Substrate binding occurs only through the pyridine nitrogen in contrast to other substrate classes exhibiting stronger substrate direction. The lack of influence of hydrogen pressure on the product enantiomeric excess suggests that a pre-equilibrium in substrate binding is maintained across the pressure range investigated. An off-cycle Rh-hydride species is implicated in the mild catalyst deactivation observed. In contrast to Ru-phosphine-catalyzed reactions of the same substrate class, the stereochemical outcome in this system correlates generally with the relative stability of the E and Z rotamers of the substrate.

Mono- and dicarbonyl-bridged tricyclic heterocyclic acceptors: synthesis and electronic properties.

A series of trialkylsilyl-substituted 2,2'-dithiophene, 4,4'-di-n-hexyl-2,2'-dithiophene, 5,5'-dithiazole, and 2,2'-diselenophene with carbonyl (2a-d) and α-dicarbonyl bridges (3a-d) were prepared from readily available dihalides, using double lithiation followed by trapping with N,N-dimethylcarbamoyl chloride or diethyl oxalate (or N,N-dimethylpiperazine-2,3-dione), respectively. Cyclic voltammetry reveals that the first half-wave reduction potentials for this series of compounds span a wide range, from -1.87 to -0.97 V vs the ferrocene/ferrocenium couple at 0 V (0.1 M (n)Bu(4)NPF(6) in THF). A significant increase of the first half-wave reduction potential (by 0.50-0.67 V) was observed on substitution of the monocarbonyl bridge with α-dicarbonyl. Adiabatic electron affinity (AEA, gas phase) trends determined via density functional theory (DFT) calculations are in good agreement with the electrochemical reduction potentials. UV-vis absorption spectra across the series show a weak absorption band in the visible range, corresponding to the HOMO→LUMO transition within a one-electron picture, followed by a more intense, high-energy transition(s). Single-crystal X-ray structural analyses reveal molecular packing features that balance the interplay of the presence of the bulky substituents, intermolecular π-stacking interactions, and S···O intermolecular contacts, all of which affect the DFT-evaluated intermolecular electronic couplings and effective charge-carrier masses for the crystals of the tricyclic cores.