Concepts In Organic Chemistry Research Articles

3,3-Difluorooxetane-A Versatile Functional Group for Bioisosteric Replacements in Drug Discovery.

Functional group (FG) is one of the cornerstone concepts in organic chemistry and related areas. The wide spread of bioisosterism ideas in medicinal chemistry and beyond caused a striking rise in demand for novel FGs with a defined impact on the developed compound properties. In this work, the evaluation of the 3,3-difluorooxetane unit (3,3-diFox) as a functional group for bioisosteric replacements is disclosed. A comprehensive experimental study (including multigram building block synthesis, quantification of steric and electronic properties, measurements of pKa, LogP, chemical stability, and biological evaluation of the 3,3-diFox-derived bioisostere of a drug candidate) revealed a prominent behavior of the 3,3-diFox fragment as a versatile substituent for early drug discovery programs.

Probing the Limit of the Number of Saturated Atoms for Achieving Hyperconjugative Aromaticity.

Aromaticity is a fundamental concept in organic chemistry. Hyperconjugative aromaticity, also known as hyperconjugation-induced aromaticity, has evolved from its origin from main group substituents to transition metal analogues, establishing itself as an important category of aromaticity. Additionally, aromatic compounds comprising two sp3-carbon atoms have recently been reported both experimentally and computationally. However, what is the maximum number of sp3-hybridized atoms needed to maintain hyperconjugative aromaticity? Here, we report that hyperconjugative aromaticity can be achieved in hexa-substituted indoliums and octa-substituted pyrroliums, possessing three-five sp3-hybridized carbon/nitrogen atoms by means of density functional theory (DFT) calculations. The aromaticity was confirmed by using various aromaticity indices, i.e., NICS, MCI, and EDDB. Notably, the strong electron-donating ability and aurophilicity of Au(I) substituents play a pivotal role in maintaining the aromaticity and structural integrity. In addition, increasing the number of hyperconjugative centers will decrease the aromaticity in these five-membered rings. Our findings highlight the significance of transition metal substituents in hyperconjugative aromaticity and offer a novel approach for designing aromatic organometallics.

Umpolung reactivity of strained C–C σ-bonds without transition-metal catalysis

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp3)-C(sp3) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs.

Examining students’ problem-solving approaches in organic chemistry and its impact on performance and learning

This research paper examines the intricacies of problem-solving (PS) in organic chemistry (OC), exploring the internal and external factors that influence students’ success in this demanding discipline. Data was collected through a questionnaire administered to 128 City College of New York students during Spring and Fall semesters of 2022. The study revealed that students face challenges learning OC, which include memorization, understanding underlying concepts, and effective PS. Notably, there is a gap between students’ professed beliefs about effective PS strategies and their actual practices. While students acknowledge the importance of techniques such as annotation, trial and error, and questioning, they inconsistently apply these strategies in practice. Annotation emerged as a valuable tool, enabling students to externalize complex thought processes and reduce reliance on memorization. Trial and error, coupled with exposure to expert PS techniques, proved effective. The role of confidence in PS was highlighted, and the need to balance memorization of reactions and rules such as naming with a profound understanding of OC concepts was emphasized. Resonance as a justification for answers underscored the importance of understanding and applying principles rather than relying solely on memorization. The data highlights the importance of aligning beliefs with actions in the learning process and the need for a balanced approach that combines knowledge with effective PS techniques. The findings offer valuable implications for educators and students seeking to enhance their performance in OC.

Effectiveness of Blended Teaching on Academic Achievement in Organic Chemistry: A case of Grade-12 Learners from an Underprivileged South African School

In South Africa, particularly in underprivileged high schools, the unavailability of resources means that the use of traditional face-to-face teaching methods that promote passive learning is prevalent. Despite a few of these schools utilising blended teaching methods that can potentially promote active learning, research that evaluates the effectiveness of these methods in promoting academic achievement is limited. Diagnostic reports on National Senior Certificate examinations of South Africa show that Grade-12 learners perform poorly in organic chemistry. Therefore, this study which was conducted during the COVID-19 pandemic, aimed to determine how effective blended teaching methods are in fostering academic achievement compared to traditional face-to-face teaching, focusing on Grade-12 organic chemistry. In this quantitative study, using Vygotsky’s socio-cultural and Maslow’s hierarchy of needs theories as the theoretical framework, two hundred learners were randomly placed into two equal groups. Group-1 (experimental) was taught all organic chemistry concepts stipulated in the South African national curriculum using a blended teaching method while Group-2 (control) was taught the same concepts using traditional face-to-face teaching method. A standardised test (KOOCT) was administered to both groups followed by descriptive and inferential statistical analyses (independent t-tests). Findings showed that Group-1 scores (M = 41.74, SD = 19.533) were higher than those for Group-2 (M = 27.18, SD = 13.039), t (198) = 6.234, p = .00 < .05 showing that using blended teaching approach was more effective in promoting academic achievement than traditional face-to-face teaching only. The effect size (Cohen’s d=.882) ensures practical significance of the study.

An Organic Chemist's Guide to Fluorophores – Understanding Common and Newer Non‐Planar Fluorescent Molecules for Biological Applications

AbstractLabeling and detection of biomolecules in vitro and in vivo is essential to many areas of biomedical science. Fluorophores stand as indispensable tools within chemical biology, underscoring the importance of fine‐tuning their optical properties. This review focuses on methods for optimizing emission wavelength, quantum yield and photostability. We focus not just on the trends, but the fundamental physical organic chemistry concepts that inform the connection between molecular structure and fluorescent properties. This approach offers an essential understanding of fluorescence, enabling readers to develop a systematic analytical framework for thinking about fluorescence. Furthermore, an evaluation of newer non‐planar fluorophores shines light on the bright future of fluorescent molecules.

Development and Rasch Analysis of the Prior Knowledge of Chemistry Concepts Test for Pre-medical Students in the Philippines

Chemistry concepts are embedded in several contexts that are related to the future professional roles of pre-medical students. In the current academic landscape of pre-medical programs, an objective measurement of prior knowledge of chemistry concepts is necessary to promote students’ academic success. To address this issue, this study aimed to develop and validate the Prior Knowledge of Chemistry Concepts Test. This multiple-choice research instrument is designed to measure pre-medical students’ knowledge of essential chemistry concepts from pre-requisite chemistry courses in pre-medical programs in the Philippines. The final item pool, consisting of 26 general chemistry concepts and 21 general organic chemistry concepts was administered to 470 college students from four tertiary institutions in the Philippines. Item content validity indices (I-CVI) and kappa statistics guided initial revisions, while dichotomous Rasch analysis was utilized to determine the psychometric properties of the research instrument. The analysis provided evidence of adequate person and item reliability, item fit, local independence, and unidimensionality, although some items may be omitted in subsequent iterations. The application of the research instrument to assessment and evaluation was elaborated using the student ability and item difficulty logits along the person-item map. Suggestions for the improvement of the research instrument were also discussed.

Nuclear quantum and H/D isotope effects on aromaticity: path integral molecular dynamics study.

Aromaticity is an important concept in organic chemistry, and thus, many theoretical and experimental studies have been conducted so far. However, the majority of theoretical studies have concentrated on the aromaticity of the stationary point structures. Herein, the influence of nuclear quantum fluctuation (nuclear quantum effects: NQEs) and thermal fluctuation on the aromaticity of benzene have been analyzed by path integral molecular dynamics (PIMD) simulation. The PIMD simulations revealed that the NQEs affected not only the C-H bonds but also the C-C bonds. The HOMA and NICS calculations demonstrated that the aromaticity decreased due to the NQEs of carbon atoms, attributed to an increase in the contribution from specific vibrational modes strongly correlated with benzene's aromaticity.

Origin of the Felkin-Anh(-Eisenstein) model: a quantitative rationalization of a seminal concept.

Quantum chemical calculations were carried out to quantitatively understand the origin of the Felkin-Anh(-Eisenstein) model, widely used to rationalize the π-facial stereoselectivity in the nucleophilic addition reaction to carbonyl groups directly attached to a stereogenic center. To this end, the possible approaches of cyanide to both (S)-2-phenylpropanal and (S)-3-phenylbutan-2-one have been explored in detail. With the help of the activation strain model of reactivity and the energy decomposition analysis method, it is found that the preference for the Felkin-Anh addition is mainly dictated by steric factors which manifest in a less destabilizing strain-energy rather than, as traditionally considered, in a lower Pauli repulsion. In addition, other factors such as the more favorable electrostatic interactions also contribute to the preferred approach of the nucleophile. Our work, therefore, provides a different, more complete rationalization, based on quantitative analyses, of the origin of this seminal and highly useful concept in organic chemistry.

Exploring diversity: student's (un-)productive use of resonance in organic chemistry tasks through the lens of the coordination class theory

Resonance is a crucial concept in Organic Chemistry that enables both deriving chemical properties from molecular structures and predicting reactions by considering electron density distribution. Despite its importance for problem-solving and learning success, learners encounter various difficulties with this concept. Although prior research suggests that learners struggle to reason about resonance in problem-solving tasks, existing studies are often limited to singular contexts. Given that task approaches and reasoning are context-dependent, little is known about how learners use resonance across task contexts and which characteristics underlie productive concept use. To this end, a qualitative interview study was conducted, in which undergraduate chemistry students (N = 21), all beginners of Organic Chemistry, solved three organic case comparison tasks requiring the consideration of resonance. Through the analytical lens of the coordination class theory, we analysed the extent to which students used their representations of resonance structures, their task approaches, and the variety of resonance-related resource activation and connection in problem-solving across three different contexts. The results show that students’ use of resonance is diverse across the contexts. It can be characterized by a complex interplay of multiple factors reflecting the multifold processes when considering resonance. However, some essential characteristics of productive concept use in problem-solving (e.g., the activation of resources across different granularity levels) could be deduced. Implications for supporting learners’ use of resonance in problem-solving are discussed.

Reactivity Umpolung of Tertiary Amide Enabled by Catalytic Reductive Stannylation.

Reactivity umpolung is an important concept in organic chemistry. Established reactivity umpolung mainly focuses on the aldehyde and umpolung of amide carbonyl group is not known. In this report, we describe a process to obtain the umpolung reactivity of tertiary amide. This process hinges on the efficient reductive stannylation catalyzed by Ir/silane and facile Sn-Li exchange. By leveraging this umpolung reactivity, drug Fluoxetine was derivatized to 12 different analogues via reacting with various electrophiles and four biologically active molecules were prepared concisely. This unlocked umpolung reactivity of tertiary amide is expected to find applications to synthesize complex amines from amides.

Reactivity Umpolung of Tertiary Amide Enabled by Catalytic Reductive Stannylation

AbstractReactivity umpolung is an important concept in organic chemistry. Established reactivity umpolung mainly focuses on the aldehyde and umpolung of amide carbonyl group is not known. In this report, we describe a process to obtain the umpolung reactivity of tertiary amide. This process hinges on the efficient reductive stannylation catalyzed by Ir/silane and facile Sn−Li exchange. By leveraging this umpolung reactivity, drug Fluoxetine was derivatized to 12 different analogues via reacting with various electrophiles and four biologically active molecules were prepared concisely. This unlocked umpolung reactivity of tertiary amide is expected to find applications to synthesize complex amines from amides.

Impact of cognitive abilities on performance in organic chemistry

Abstract The purpose of this study was to observe the relationship between students’ cognitive abilities and their performance in organic chemistry. We were interested in measuring whether some cognitive composites were more predictive than others on organic chemistry performance, whether group differences existed between males and females, and whether group differences existed between students with above and below average cognitive abilities. For Study 1 and Study 2, our participants included 48 and 60 sophomore organic chemistry students respectively. We used the Woodcock-Johnson Test of Cognitive Abilities-IV to measure cognitive composites. ACS organic chemistry exam scores and scores on an organic chemistry concept inventory were used to measure student performance. We ran a correlational analysis between the cognitive composites and organic chemistry scores, and t-tests for group comparisons. For Study 1, we found a significant moderate correlation between long-term retrieval and organic chemistry scores. For Study 2, we found a significant small to moderate correlation between comprehension knowledge and short-term working memory, with organic chemistry scores. We did not find any significant gender differences, except on comprehension knowledge. The differences between above average and below average cognitive abilities were only seen in relation to the concept inventory and not ACS exam scores.

Redesigning an organic laboratory course for remote learning: incorporating Lab@Home kits and other techniques for teaching organic chemistry online

Many cities in the world were placed under various lockdowns to combat the spread of the COVID-19 pandemic, which also forced many schools to shift into full online mode of teaching and learning. In the Philippines, partial onsite classes only resumed after nearly 2 years of strict online classes. Of critical concern then was the teaching of laboratory courses. This necessitated the re-design of the usual laboratory experiments to a Lab@Home course to provide a semester’s worth of an organic laboratory course to college students of the Ateneo de Manila University. Here, we present a Lab@Home curriculum that covers core organic chemistry concepts, such as purification and separation of organic compounds, reactivity and qualitative tests, stereochemistry, and molecular spectroscopy (IR and NMR). This Lab@Home course involved sending boxed kits containing laboratory materials and reagents that allowed students at home to perform small-scale experiments. Aside from reinforcing key concepts in the accompanying lecture class, it also provided them with experiential learning of practical laboratory techniques such as setting up an experiment and real data collection. Safety first is maintained, and aside from providing the usual protective gear, safety is further assured with two important features: (1) the hazards classification of the reagents in the kit would not exceed the everyday life hazards of common household chemicals (e.g., kitchen cleaning reagents) and provided in very small amounts, and (2) running of experiments were done with online synchronous supervision majority of the time. The success of the course is the achievement of the CLOs, from the assessments as well as from feedback taken from surveys and interviews with students and instructors at the end of the semester. Overall student performance showed an average final grade of 85%, and student response to the curriculum was generally positive. Further improvements should be implemented to make experiments more enriching and ensure Lab@Home can become an effective tool for teaching remote laboratory classes.

Bioorthogonal Metabolic Labeling Experiments to Introduce Undergraduate Students to Interdisciplinarity at the Interface of Chemistry and Biology

Chemists have always designed and deployed cross-disciplinary approaches that interface chemistry with other disciplines to proffer solutions to many human problems. We designed a laboratory experiment that implements chemistry concepts in a biological model to prime undergraduate students to appreciate interdisciplinarity as an approach to solving complex problems in contemporary society. The experiments can also be implemented with graduate students transitioning to chemical biology research. The experiment introduces students to classical and emerging chemistry and molecular biology techniques─mammalian cell culture, bioorthogonal metabolic labeling, azide–alkyne cycloaddition reaction (“click” chemistry), microplate photometry, gel electrophoresis, and far-western blot analysis─that are routinely used in research at the interface of chemistry and biology. The students cultured a Chinese hamster ovary cell line (CHO-K1) and metabolically labeled the cellular sialoglycans with azide groups. Next, they used a click chemistry reaction to bioconjugate a fluorogenic molecule to the labeled sialoglycans, enabling the detection of the glycans using microplate photometry or far-western blot analysis. The experiment created a context for a first-hand demonstration of bioorthogonal chemical reaction, a concept novel to most undergraduates with traditional chemistry (organic, inorganic, physical chemistry, and analytical) background. The experience allows the students to apply and connect organic chemistry, bioanalytical chemistry, and molecular biology concepts while learning techniques such as microplate reading, SDS PAGE, and western blot imaging that are indispensable to the growing fields of drug discovery, chemical toxicology, chemical biology, and molecular biology. This experiment is ideal for preparing and motivating students to pursue future research opportunities at the interface of chemistry and biology.

Biochemical Symmetrization/ Desymmetrization of Organic Compounds: Dendrimeric Relationship with Molecular Formulas

A criterion for systematization of organic compounds is described. Organic compounds (estimated to 16-20 millions) are of three types: (A) symmetric (especially meso and C2 symmetric), (B) possible symmetry generators, i.e. compounds possessing a real or imaginary, but plausible, symmetric correspondent: irrechi (from irregular distribution of chiral carbons) and constitutional), and (C) archaic (or primitive) that are neither symmetric nor possible symmetry generators. Symmetric compounds are a minority in organic chemistry. The three groups are (bio) chemically interchangeable. In preceding papers we have demonstrated that almost all natural micromolecular combinations are either symmetric or possible symmetry generators; archaic (primitive) type is also represented in natural chemistry. On the other hand, it should be stressed that symmetric compounds, both meso and C2 symmetrical (C2 symm.) have been found almost exclusively in plants and microorganisms, and they are usually produced from constitutional (constit.) precursors. A series of symmetrization/desymmetrization reactions are presented, and the proof is evidenced that they can establish a new and coherent concept in biochemistry and organic chemistry. Symmetrization reactions can be followed according to chemical type involved: oxidation, cyclization, esterification, glycosylation, methylation, etc. This approach is valid to all major classes of compounds. A dendrimeric relationship is presented within molecular formulae.

Phosphole aromaticity enhancement by electron pumping through Schleyer hyperconjugative aromaticity: A comprehensive DFT study

Combination of aromaticity and hyperconjugation as two fundamental concepts in organic chemistry results hyperconjugative aromaticity. Due to trigonal pyramidal P (III) atom in phosphole ring, it is only slightly more aromatic than cyclopentadiene. In the present work, the hyperconjugative aromaticity of phosphole derivatives, bearing an electron donating group, have been studied at the DFT-B3LYP/6–311++G(d, p) level of theory using various aromaticity indices such as geometric, magnetic, electronic and energetic criteria. Our DFT calculations reveal that an electropositive substituent can enhance phosphole aromaticity through Schleyer hyperconjugative aromaticity. This hyperconjugative electron donation by the substituents results in a partially anionic phosphole ring. Among the electropositive groups, silyl and germanium substituents have the best performance. The excellent correlations are observed between all aromaticity indices. Our findings could help chemists to design novel hyperconjugative aromatic phospholes.

Do-It-Yourself 5-Color 3D Printing of Molecular Orbitals and Electron Density Surfaces

This report outlines an approach for preparing 5-color 3D printed plastic models of molecular orbitals and electron density surfaces using a hobby-grade 3D printer. Instructions are provided for preparing 3D orbital and electron density surface (EDS) models using solid or mesh representations in ground state and transition state structures. We show that the information content of 3D orbital and surface models can be enhanced with text annotation, bisection, strut and dashed bond placement, and composite orbital-EDS model constructions. Example prints illustrate orbital concepts in organic and inorganic chemistry, such as the ethyl cation (σ–p hyperconjugation), methane (hybridization and C–H bonding), ethane (σ–σ* hyperconjugation in the staggered and eclipsed conformations), 2-hydroxytetrahydropyran (the anomeric effect/n−σ* hyperconjugation), the water dimer (hydrogen bonding/n−σ* overlap), ethylene, 1,3-butadiene, and benzene (π molecular orbitals), Re2Cl82–, and U2(COT)2 (metal–metal quadruple bonds). Transition state models illustrate orbital interactions in the SN2 reaction of cyanide with methyl, ethyl, and isopropyl chloride and in a hydroboration reaction of BH3 with propene. Composite EDS models of methyl and isopropyl chloride (for exploring their relative reactivities as SN2 electrophiles) and methylcyclohexane (visualizing 1,3-diaxial interactions) are described. Student perceptions of a multicolor 3D orbital print used in an introductory organic chemistry laboratory course are reported.

Identification of Local Wisdom of The Sasak Tribe In Chemistry Learning as an Effort to Strengthen Student Character

Globalization has a negative impact on local wisdom and the character of the successor of the Indonesian nation. It causes the culture of other countries to influence local wisdom so that it experiences a shift and slowly disappears. It triggers youth violence and erodes morals, character, sense of humanity, and nationalism. Students who are dominated by the Sasak tribe are currently less familiar with their traditions and culture. The solution to this problem is to integrate local wisdom into formal chemistry learning. This study aims to identify local wisdom of the Sasak tribe that can be integrated in chemistry learning. The approach used in this research is qualitative. The research sample is cultural practitioners and the Sasak people. Sampling using purposive technique. The implementation of this research consists of four stages based on data analysis of the Miles and Huberman Model, namely data collection, data reduction, data presentation, and drawing conclusions. The data collection technique is triangulation, which combines interviews, observations, and documents. The results of this study are local wisdom of the Sasak tribe that can be integrated in chemistry learning. The local wisdom includes mopping with cow dung, dilah jojor, nyesek, and gendang beleq. The results of the analysis of local wisdom show that there is relevance to chemistry, namely the concepts of organic compounds, inorganic compounds, chemical bonds, elemental chemistry, instrument analysis, chemical separation, and chemistry of natural materials. The integration of local wisdom into chemistry learning has an impact on maintaining the existence of local wisdom of the Sasak tribe as well as strengthening the character of students

The Effect of Argumentation-Based Organic Chemistry Teaching on Students’ Argument Construction Skills

Some students could not learn organic chemistry because of the difficulty of its submicroscopic nature. In this study, it was aimed to determine the effect of argumentation-based organic chemistry teaching on high school students’ argument construction skills so on their meaningful concept learning. The study was conducted on 14 high school students at a vocational high school in Turkey on organic chemistry topics through 28 hours period based on the case study. The teaching guide’s worksheets and students’ observation notes were used as data collection tools. Through the application process, the students criticized each of the seven submicroscopic nature of organic chemistry concepts’ paintings in big group discussions, then constructed their own arguments. Then the students evaluated the whole process. Content analysis was employed for the data analysis. Argumentation making students criticize the submicroscopic nature of organic chemistry resulted in a qualified student-constructed argument by making them understand the submicroscopic nature so become critical thinkers. Students’ process evaluation also underlined that the process made students joyful, motivated, creative, criticizer, and meaningful learners with a differently constructed learning environment. For further studies, different argumentation-based organic chemistry teaching environments could be offered.
 Anahtar Kelimeler
 Chemistry teaching, submicroscopic nature of chemistry, argumentation, critical thinking