Synthesis and release behavior of layered double hydroxides–carbamazepine composites

Carbamazepine (CBZ) was incorporated into layered double hydroxides (LDH) to be used as a controlled drug system in solid tumors. CBZ has a formal charge of zero, so its incorporation in the anionic clay implies a challenge. Aiming to overcome this problem, CBZ was loaded into LDH with sodium cholate (SC), a surfactant with negative charge and, for comparison, without SC by the reconstruction method. Surprisingly, it was found that both resultant nanocomposites had similar CBZ encapsulation efficiency, around 75%, and the LDH-CBZ system without SC showed a better performance in relation to the release kinetics of CBZ in simulated body fluid (pH 7.4) and acetate buffer simulating the cellular cytoplasm (pH 4.8) than the system with SC. The CBZ dimensions were measured with Chem3D and, according to the basal spacing obtained from X-ray patterns, it can be arranged in the LDH-CBZ system as a monolayer with the long axis parallel to the LDH layers. Fourier transform infrared spectroscopy and solid state NMR measurements confirmed the presence of the drug, and thermogravimetric analyses showed an enhanced thermal stability for CBZ. These results have interesting implications since they increase the spectrum of LDH application as a controlled drug system to a large number of nonionic drugs, without the addition of other components.

Chemical Bonding 1: Basic Concepts

Chemical Bonding I: Basic Concepts examines general ideas of chemical bonding between atoms and ions and how this bonding affects the chemical properties of the elements. An overview of Lewis symbols, Lewis structures and the octet rule is presented including the role of valence electrons in ionic and covalent bonding. The energy changes that accompany ionic bond formation are also discussed with emphasis on lattice energy. The chapter covers guidelines and general procedures for writing Lewis structures or electron dot formulas for molecular compounds and polyatomic ions. The concepts and applications of resonance, formal charge and exceptions to the octet rules are presented, along with coverage of the relationship between bond polarity and electronegativity.

Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2LOO 0.57, respectively) and the test set (5% and Q2test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.

Identifikasi miskonsepsi materi ikatan kovalen pada mahasiswa kimia tahun pertama universitas negeri malang menggunakan tes diagnostik two-tier

The concept of chemistry must be well understood because the concept of chemistry is hierarchical and sequential. In addition, the concept of chemistry is abstract, which can provoke misconceptions. This study aims to identify misconceptions about the covalent bonding material and to determine the percentage of misconceptions about these materials. The results showed that a misconception was observed in 10 concepts of covalent bonding material with the following percentages: 1) 23 percent of the concepts forming elements of covalent compounds, the covalent compounds must be composed of non-metallic elements with non-metallic elements; 2) 69 percent on the Lewis structure concept, the total number of electrons based on the Lewis structure drawing is the number of valence electrons; 3) 54 percent in the concept of double bonds, the breaking energy of the double bonds is twice that of the energy of the single bonds; 4) 35 percent on the concept of covalent coordination bonds, the covalent coordination bonds are shorter than the covalent bonds; 5) 54 percent on the concept of polar covalent bonds and molecular polarity, the pair of binding electrons is located at the same distance between two bonding atoms; 6) 27 percent in the concept of formal charge, the value of the influences of electronegativity in the determination of the formal charge; 7) on the notion of byte rule and the stability of covalent compounds, 27 percent of the stable Lewis structure does not have a free electron pair (PEB) and respects the byte rule; 62 percent chlorine gas will form the Cl2 molecule because it follows the octet rule; and 54 percent of the covalent bonds store chemical energy; 8) 42 percent on the concept of molecular form, the molecular form of a compound is determined by the repulsion of binding electron pairs; 9) on the concept of intermolecular forces and the properties of covalent compounds, 38 percent of the energy required to boil the table salt is superior because the table salt is an ionic bond; and 81 percent of the strongest interactions are hydrogen bonds; and 10) in the concept of valence bond theory, 23 percent of the most important particles in the formation of covalent bonds are valence electrons; and 27 percent electron sharing means sharing one (1) electron with two atoms, as in the case of sharing an apple for two people. Konsep ilmu kimia perlu dipahami dengan baik, karena konsep ilmu kimia berjenjang dan berurutan. Selain itu, konsep ilmu kimia bersifat abstrak, sehingga dapat menyebabkan miskonsepsi. Penelitian ini bertujuan untuk mengidentifikasi miskonsepsi pada materi ikatan kovalen dan mengetahui persentase miskonsepsi pada materi tersebut. Hasil penelitian menunjukkan bahwa miskonsepsi terjadi pada 10 konsep materi ikatan kovalen dengan persentase sebagai berikut: 1) 23 persen pada konsep unsur-unsur pembentuk senyawa kovalen, senyawa kovalen harus tersusun atas unsur non logam dengan unsur non logam; 2) 69 persen pada konsep struktur Lewis, elektron total berdasarkan gambar struktur Lewis adalah jumlah elektron valensi; 3) 54 persen pada konsep ikatan rangkap, energi pemutusan ikatan rangkap dua kali lipat daripada energi pemutusan ikatan tunggal; 4) 35 persen pada konsep ikatan kovalen koordinasi, ikatan kovalen koordinasi lebih pendek daripada ikatan kovalen; 5) 54 persen pada konsep ikatan kovalen polar dan kepolaran molekul, pasangan elektron ikatan terletak pada jarak yang sama diantara dua atom yang berikatan; 6) 27 persen pada konsep muatan formal, nilai elektronegativitas berpengaruh dalam menentukan muatan formal; 7) pada konsep aturan oktet dan kestabilan senyawa kovalen, 27 persen struktur Lewis yang stabil tidak memiliki Pasangan Elektron Bebas (PEB) dan memenuhi aturan oktet; 62 persen gas klorin akan membentuk molekul Cl2 karena memenuhi aturan oktet; dan 54 persen ikatan kovalen menyimpan energi kimia; 8) 42 persen pada konsep bentuk molekul, bentuk molekul suatu senyawa ditentukan tolakan pasangan elektron ikatan; 9) pada konsep gaya antar molekul dan sifat-sifat senyawa kovalen, 38 persen energi yang dibutuhkan untuk mendidihkan garam dapur lebih besar karena garam dapur merupakan ikatan ionik; dan 81 persen interaksi tarik-menarik yang paling kuat adalah ikatan hidrogen; dan 10) pada konsep teori ikatan valensi, 23 persen partikel paling penting dalam pembentukan ikatan kovalen adalah elektron valensi; dan 27 persen sharing electron berarti pemakaian bersama 1 (satu) elektron oleh dua atom, seperti pada kasus berbagi sebuah apel untuk dua orang.

Heuristics Hindering the Development of Understanding of Molecular Structures in University Level Chemistry Education: The Lewis Structure as an Example

Understanding chemical models can be challenging for many university students studying chemistry. This study analysed students’ understanding of molecular structures using the Lewis structure as a model, and examined what hinders their understanding. We conducted pre- and post-tests to analyse students’ conceptions and changes in them. The measures contained multiple-choice questions and drawing tasks testing their understanding of concepts, such as polarity, geometry, charge or formal charge and expanded octet. The pre-test revealed a lack of knowledge and several misconceptions in students’ prior knowledge. For example, the concept of polarity was well-known, but the combination of polarity and geometry appeared to be difficult. For some students, the representation of molecules was intuitive and lacking a systematic approach. Certain students used mnemonics and draw ball-and-stick models connected to surficial representations. After the chemistry courses, the conceptions and drawings had generally changed, and the level of the students’ knowledge increased markedly. Although, fewer ball-and-stick models were drawn in the post-test, some students still used them. The main result was that students who drew ball-and-stick models in the pre-test were less capable of drawing the correct Lewis structures with electrons in the post-test. In addition, heuristics seem to hinder learning and some concepts, such as resonance, remained difficult. This is probably due to the fact that understanding molecular structures requires systemic understanding, where several matters must be understood at the same time. Our study highlights that the understanding of molecular structures requires conceptual change related to several sub-concepts.

Cluster Models of FeMoco with Sulfide and Carbyne Ligands: Effect of Interstitial Atom in Nitrogenase Active Site

<p>Nitrogen-fixing organisms perform dinitrogen reduction to ammonia at an iron-M (M = Mo, Fe, or V) cofactor (FeMco) of nitrogenase. FeMoco displays eight metal centers bridged by sulfides and a carbide having the MoFe₇S₈C cluster composition. The role of the carbide ligand, a unique motif in protein active sites, remains poorly understood. Toward addressing its function, we isolated synthetic models of subsite MFe₃S₃C displaying sulfides and a carbyne ligand. We developed synthetic protocols for structurally related clusters, [Tp*MFe₃S₃X]^n-, where M = Mo or W, the bridging ligand X = CR, N, NR, S, and Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate, to study the effects of the identity of the heterometal and the bridging X group on structure and electrochemistry. While the nature of M results in minor changes, the μ₃-bridging ligand X has a large impact on reduction potentials, with differences higher than 1 V, even for the same formal charge, the most reducing clusters being supported by the carbyne ligand. </p>

Cluster Models of FeMoco with Sulfide and Carbyne Ligands: Effect of Interstitial Atom in Nitrogenase Active Site

<p>Nitrogen-fixing organisms perform dinitrogen reduction to ammonia at an iron-M (M = Mo, Fe, or V) cofactor (FeMco) of nitrogenase. FeMoco displays eight metal centers bridged by sulfides and a carbide having the MoFe₇S₈C cluster composition. The role of the carbide ligand, a unique motif in protein active sites, remains poorly understood. Toward addressing its function, we isolated synthetic models of subsite MFe₃S₃C displaying sulfides and a carbyne ligand. We developed synthetic protocols for structurally related clusters, [Tp*MFe₃S₃X]^n-, where M = Mo or W, the bridging ligand X = CR, N, NR, S, and Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate, to study the effects of the identity of the heterometal and the bridging X group on structure and electrochemistry. While the nature of M results in minor changes, the μ₃-bridging ligand X has a large impact on reduction potentials, with differences higher than 1 V, even for the same formal charge, the most reducing clusters being supported by the carbyne ligand. </p>

Perrierite-(Ce) from the Laacher See tephra, Eifel, Germany, and the modular character of the chevkinite group of minerals

Perrierite-(Ce) crystals from ejecta of the Laacher See volcano, Eifel, in Germany were studied by X-ray single-crystal diffraction and electron microprobe analysis. The composition and crystal structure of this sample is discussed in relation to the known properties of the chevkinite group minerals and related synthetic compounds. Taking into account the modular character of the chevkinite minerals, based on a rutile and a silicate module, the preferred formation of either the perrierite or the chevkinite structure type is correlated with the formal charge of the rutile and silicate modules. The rutile module is expected to carry a negative charge, compensated by a positive charge of the silicate module. On average, the charge modulus is observed to be larger for the chevkinite-type module stacking. It can drop to zero in perrierite-type structures rich in Sr or Ca. In such cases, it is generally not expected to rise above two. The perrierite-(Ce) described in this study crystallizes in space group C2/m. The anisotropic oxygen and rare-earth element displacements observed in this crystal indicate a local domain structure of $$P2_1/a$$ P 2 1 / a symmetry, when compared to the $$P2_1/a$$ P 2 1 / a symmetry of the synthetic perrierite $$\hbox {La}_4\hbox {Mg}_2\hbox {Ti}_3\hbox {O}_8(\hbox {Si}_2\hbox {O}_7)_2$$ La 4 Mg 2 Ti 3 O 8 ( Si 2 O 7 ) 2 .

Synthesis and release behavior of layered double hydroxides – carbamazepine composites

Carbamazepine (CBZ) was incorporated into Layered Double Hydroxides (LDH) to be used as controlled drug delivery in solid tumors. CBZ has a formal charge of 0, which implies a challenge to be incorporated in the anionic clay. Aiming to overcome this problem, CBZ was first incorporated in micelles of sodium cholate (SC), a surfactant with negative charge. CBZ in SC micelles and, for comparison, free CBZ were incorporated in LDH by reconstruction method. It was found that resultant nano-composites had similar CBZ encapsulation efficiency, around 75 %, but drug release in simulated body fluid (pH 7.4) and acetate buffer (pH 4.8) was efficient only with the LDH-CBZ sample. CBZ dimensions were measured with Chem3D and, according to the basal spacing obtained from X rays patterns, it can arrange as monolayer with the long axis parallel to the LDH layers. Fourier Transform Infrared Spectroscopy confirmed the incorporation of the drug. Thermogravimetric analyses showed and enhanced thermal stability for CBZ. These results have interesting implications since they increase the spectrum of LDH application as controlled drug delivery to a large number of non-ionic drugs, without the addition of other components.

Refining physico-chemical rules for herbicides using an antimalarial library

ABSTRACTSuccessful herbicides, like drugs, have physico-chemical properties that usually fall within certain limits. A recent analysis of 334 herbicides showed similar properties to the ‘rule of five’ for human orally-delivered drugs, but herbicides diverged from this for proton donors, partition coefficients and molecular weight. To refine rules for herbicides, we exploited the close evolutionary relationship between P. falciparum and plants by screening the Malaria Box, a 400-compound library composed of novel chemical scaffolds with activity against blood stage malaria parasite Plasmodium falciparum. A high proportion (52 of 400) were herbicidal to Arabidopsis thaliana on agar plates. Thirty-nine of these 52 herbicidal compounds were tested on soil and 16 compounds were herbicidal. These data were used to predict whether a herbicidal hit found on agar will work on soil-grown plants. The physico-chemical parameters were weighted to logP and formal charge and used to generate weighted scores to a large chemical library of liver-stage effective antimalarial leads. Of the six top-scoring compounds, one had a potency comparable to commercial herbicides. This novel compound MMV1206386 had no close structural matches among commercial herbicides. Physiological profiling suggested that MMV1206386 has a new mode of action and overall demonstrates how weighted rules can help during herbicide discovery programs.