Synthetic Studies Research Articles

Zeolite encapsulated organometallic complexes as model catalysts.

Heterogeneities in the structure of active centers in metal-containing porous materials are unavoidable and complicate the description of chemical events occurring along reaction coordinates at the atomic level. Metal containing zeolites include sites of varied local coordination and secondary confining environments, requiring careful titration protocols to quantify the predominant active sites. Hybrid organometallic-zeolite catalysts are useful well-defined platform materials for spectroscopic, kinetic, and computational studies of heterogeneous catalysis that avoid the complications of conventional metal-containing porous materials. Such materials have been synthesized and studied previously, but catalytic applications were mostly limited to liquid-phase oxidation and electrochemical reactions. The hydrothermal stability, time-on-stream stability, and utility of these materials in gas-phase oxidation reactions are under-studied. The potential applications for single-site heterogeneous catalysts in fundamental research are abundant and motivate future synthetic, spectroscopic, kinetic, and computational studies.

Synthetic and mechanistic study on the conjugate isothiocyanation of enones with trimethylsilyl isothiocyanate.

Alkyl isothiocyanates (R-NCS) have pharmacological applications and provide a synthetic handle to various functional groups including thioureas. There are however few methods to access alkyl isothiocyanates through the creation of the C-N bond. We have developed a simple approach for the conjugate isothiocyanation of enones by trimethylsilyl isothiocyanate (TMSNCS), which proceeds through the 1,4-addition of the weak isothiocyanate nucleophile to activated enones in the absence of external promoters. This method avoids the direct use of highly toxic acids and bases, produces β-isothiocyanato carbonyl products in yields of 87-98% under mild conditions (less than 6 hours at 0 °C), and displays wide functional group tolerance. Density functional theory calculations highlighted competing cationic and anionic mechanisms, where the enone activation by the TMSNCS reagent is accelerated in protic solvents. The selective formation of the isothiocyanate vs. thiocyanate isomers is explained by the thermodynamically-controlled nature of the reaction in which only the conjugate isothiocyanation is exergonic.

War and Entrepreneurship: A Synthetic Control Study of the Russia-Ukraine Conflict

War and Entrepreneurship: A Synthetic Control Study of the Russia-Ukraine Conflict

The Economic Costs of the Russia-Ukraine War: A Synthetic Control Study of (Lost) Entrepreneurship

The Economic Costs of the Russia-Ukraine War: A Synthetic Control Study of (Lost) Entrepreneurship

Cyclic alkyl(amino)iminates (CAAIs) as strong 2σ,4π-electron donor ligands for the stabilisation of boranes and diboranes(4): a synthetic and computational study.

Singly and doubly cyclic alkyl(amino)iminate (CAAI)-substituted boranes and diboranes(4) were synthesised by halosilane elimination between a silylimine and halo(di)borane precursors. 11B NMR-spectroscopic studies show that the CAAI ligand is a much stronger electron donor than amino ligands. X-ray crystallographic analyses reveal that the degree of B-NCAAI double bonding increases with the electron-withdrawing capacity of the other substituents at boron. The C-N-B bond angle displays a great flexibility, ranging from 131° to near-linear 176°, the narrowest angles being observed for NMe2-substituted derivatives and the widest angles for highly sterically demanding substituents. Density functional theory (DFT) calculations on the electronic structures of the anionic CAAI ligand compared to unsaturated and saturated N-heterocyclic iminate (NHI) ligands show that the former is the best σ donor of the three but less π-donating than the unsaturated NHI. Nevertheless, the linear (CAAI)BH2 complex displays somewhat stronger C-N and N-B π bonding than the corresponding ((S)NHI)BH2 complexes.

Microwave synthesis of cationic ABAB di-imidazolyl fluorinated porphyrins and manganese complexes

ABAB porphyrins are promising platforms for potential use in several applications, particularly in medical imaging. Herein, the synthetic optimization studies for preparing such porphyrins via the statistical condensation of 4-trifluoromethylphenyl and 1-methylimidazol-2-yl aldehydes with pyrrole, are described, with emphasis on the use of microwave irradiation as heating source, against conventional heating. Then, the preparation of the corresponding Mn(III) complex and cationization of the imidazole groups, using microwave irradiation, were also carried out and the photophysical, photochemical, and electrochemical properties were further assessed. The compounds revealed interesting features, including adequate log P, singlet oxygen yield, redox potentials, and excellent photostability, which pave the way for potential use as imaging probes in MRI or PET, or as photosensitizing molecules.

Support studies toward the hicksoane alkaloids reveal cascade reactions of a (tryptophanamido)methylglycinate.

Herein we report unanticipated results that emerged from a synthetic study targeting the unique triazocane present in the hicksoane alkaloids. An initial strategy focused on the cyclisation-ring expansion of a 3-(tryptophyl)imidazolidin-4-one failed due to the high reactivity of the imide unit; passing a methanolic solution of this compound through a weakly basic ion exchange resin led to methanolysis to form a (tryptophanamido)methylglycinate. Attempted lactamisation of this (tryptophanamido)methylglycinate led to the formation of a (tryptophyl)imidazolidin-4-one, a rare imidazopyrido[3,4-b]indolone and a β-carboline. Control reactions informed a mechanistic rationale for these cascade processes.

Nucleic acids as templates and catalysts in chemical reactions: target-guided dynamic combinatorial chemistry and in situ click chemistry and DNA/RNA induced enantioselective reactions.

Nucleic acids play crucial roles in transferring cellular information and gene regulations. DNA and RNA molecules have been associated with multiple human diseases and thus offer opportunities for exploring small molecule-based therapeutics. However, developing target-selective molecules possessing well-defined biological activity, has always been challenging. In the current scenario, where the world is continuously experiencing outbreaks of new infectious diseases, it is always important to expand the scope of chemical toolsets to override conventional drug discovery strategies for developing therapeutically relevant drug candidates. The template-directed synthetic approach has emerged as a promising tool for rapid drug discovery. It allows a biological target to template the selection or synthesis of its ligands from a pool of reactive fragments. There are two main template-directed synthetic strategies: thermodynamically controlled dynamic combinatorial chemistry (DCC) and kinetically controlled target-guided in situ click chemistry. Though discovered only two decades ago, these techniques have proven their usefulness for nucleic acid targets, as exemplified by the increasing number of applications with therapeutically important DNA and RNA targets. However, nucleic acid templated synthetic techniques are relatively unexplored in drug discovery compared to protein targets. In this review article, we have presented a detailed discussion of all the reported nucleic acid templated synthetic studies to portray the great potential of this strategy for efficient hit discovery and lead optimisation. This article would assist in expanding the scope and utility of this strategy through a summary of the advancements and emerging applications. Additionally, a brief overview of the catalytic potential of nucleic acids in asymmetric synthesis has been provided to give a valuable vision of the use of nucleic acids to induce enantioselectivity in chiral drug-like candidates.

SYNTHETIC STUDY OF Pc-2, AN ACTIVE COMPOUND FROM INDONESIAN RED BETEL LEAF

PC-2 is one of the active compounds isolated from Indonesian red betel leaf. The structure of the compound is named 2-allyl-4-(1'-hydroxy-1'-(3",4",5"-trimethoxyphenyl)propan-2'-yl)-3,5-dimethoxycyclohexa-3,5-dienone and included in the neolignan’s structure category. This compound was reported to have very good biological activity in giving antiproliferative effects on human breast (T47D) cells. From 2.12 g of its leaf methanolic extract, only 12.1 mg of Pc-2 was collected. This amount is too small to do more studies about its biological activities. The synthetic work should be applied to get a sufficient amount. This paper is aimed to explain the synthetic study and design of the Pc2 compound. The first approach is by involving the aldol reaction in the synthetic pathway through the disconnection approach. The result showed that this attempt did not work very well. The second approach is to design the new synthetic pathway by using the synthia Organic Retrosynthesis Software by Merck. This software gave a reasonable result to be tried. The result proposed the use of the Suzuki coupling reaction for the new synthetic pathway of Pc-2.

Multi-platform synthesis of ondansetron featuring process intensification in flow

The synthetic studies of ondansetron by a multi-platform, built-for-purpose approach were presented. The studies highlighted the complementary strengths of batch and flow approaches to API synthesis.

Studia operacyjne w Wojsku Polskim w latach 1921–1939. Stan badań

The issue of operational studies, or war planning, during the Second Polish Republic has aroused limited research interest since the end of the Polish campaign of 1939 that ended in defeat. This paper analyses the current achievements of Polish historiography regarding this topic – not limiting itself only to the literature created after 1989 – whilst also highlighting gaps in the research that need filling. The article presents, on the one hand, a synthetic study of the problems associated with war planning between 1921–1939 and, on the other a text in the field of historio graphy.

Marmora Bizantina: A digital corpus of marble finds from the southern Levant

Archaeological excavations in the Levant have provided a significant number of marble finds dated to the early Byzantine period (4th – mid-7th century CE). Information on these objects is, however, scattered over numerous publications, hindering synthetic studies of marble imports that reached this part of the Mediterranean world. A way to address this problem was to create a database facilitating access to the dataset of marble finds from the southern Levant. This paper presents the Marmora Bizantina database, describes its content and interface, and discusses the geographic and chronological scope of the dataset. Some uses of the database are discussed, remarking on the limitations that need to be taken into account. The paper also provides information on the analytical tools available on the database website.

DESIGN, SYNTHESIS, AND PHARMACOLOGICAL EVALUATION OF NOVEL BIS-INTERCALATORS AS POSSIBLE ANTICANCER AGENTS

An attempt is made to design, synthesize and pharmacologically evaluate novel bis-intercalators as possible anticancer agents. According to a literature study on bis-intercalators, 4-substituted bis-benzamides are widely recognized for their medicinal uses and may be effective anticancer and antioxidant agents. Synthetic studies revealed that the yield of Chain linkers L1-L14, 4-substituted bis benzamides, and L-proline derivatives were in the 50-70% range. The 4-substituted bis benzamides compounds have been evaluated for anticancer and antioxidant activity studies. Among the 4-substituted bis benzamides compounds, Compound IIIc, IIIf, and IIIg have revealed promising anticancer and antioxidant activity. Compounds III7 and III12 have good cytotoxicity and antioxidant activity among L-proline derivatives. As a result, the current study emphasizes the significance of 4-substituted bis benzamides and L-proline derivatives with various heterocyclic moiety features responsible for cytotoxicity and antioxidant activity. It might be a starting point for further alterations to create new entities with therapeutically useful properties.

STUDIES ON THE AGRARIAN HISTORY OF POLAND (BASED ON THE MATERIALS OF THE MAGAZINE “KWARTALNIK HISTORYCZNY” OF THE END OF THE 19th – BEGINNING OF THE 20th CENTURY)

The purpose of the research is to reveal how the process of formation and development of Polish agrarian history studies was refl ected in the pages of the journal “Kwartalnyk Historyczny” in the general context of historical and economic research – a new research direction for Polish historiography at that time. The research methodology is based on the principles of historicism, systematicity, scientifi city, verifi cation, authorial objectivity, moderate narrative constructivism, as well as the use of general scientifi c (analysis, synthesis, generalization) and special-historical (historical-genetic, historical-typological, historicalsystemic ) methods. The scientifi c novelty is that, for the fi rst time in historiography, an attempt was made to reconstruct the process of formation and development of research on the agrarian history of Poland on the pages of the journal “Kwartalnik Historyczny” (1887–1918). Conclusions. The study of the publications of the journal “Kwartalnik Historyczny” shows that the history of the Polish economy has long been closely connected with the refl ection on the past of Polish society and the state system. Demarcation of issues in many points was simply impossible, since the state system conditioned socio-economic relations, on the other hand, the impulses of changes in the fi eld of law and administration were dependent on society. Historians specializing in these fi elds had to take all these factors into account. This entailed the need to expand the view of the problems of the past and move to another level of research - from positivist micrographic studies to generalizing, synthetic studies, which, in turn, led to the modernization of existing models of historical knowledge and brought historical science to a higher, more generalizing level of understanding the past.

Three-Component Reaction of 3-Formyl-6-Methylchromone, Primary Amines, and Secondary Phosphine Oxides: A Synthetic and Mechanistic Study.

A fast, mild, and efficient catalyst-free approach has been developed for the synthesis of chromonyl-substituted α-aminophosphine oxides by the three-component reaction of 3-formyl-6-methylchromone, primary amines, and secondary phosphine oxides at ambient temperature. Carrying out the reaction with aliphatic amines or aminoalcohols at a higher temperature (80 °C), phosphinoyl-functionalized 3-aminomethylene chromanones were formed instead of the corresponding chromonyl-substituted α-aminophosphine oxides. No reaction occurred when 3-formyl-6-methylchromone and secondary phosphine oxides were reacted with aromatic amines in the absence of any catalyst. Applying a basic catalyst, the formation of the phosphinoyl-functionalized 3-aminomethylene chromanones was observed; however, the reaction was not complete. Detailed experimental and quantum chemical studies were performed to study the transformation. Moreover, the in vitro cytotoxicity of phosphinoyl-functionalized 3-aminomethylene chromanones was also investigated in three different cell lines, such as human lung adenocarcinoma (A549), mouse fibroblast (NIH/3T3), and human promyelocytic leukemia (HL60) cells. Several derivatives showed modest activity against the human promyelocytic leukemia (HL60) cell line.

Development of a 1D/2D Urban Flood Model Using the Open-Source Models SWMM and MOHID Land

Urban pluvial floods are the outcome of the incapacity of drainage systems to convey the runoff generated by intense rainfall events. Cities have been struggling to control such hazards due to several pressures, such as urbanization increase, more frequent experiences of extreme rainfall events, and increases in tide levels. Such pressures demand the study of adaptation strategies, which conventional one-dimensional drainage models fall short of simulating. Thus, 1D/2D models have been emerging with the aim of allowing better integration of key processes for flood modeling, namely, runoff interception by stormwater inlet devices and manhole overflows. The current paper presents a 1D/2D urban flood model based on an offline coupling procedure between the 1D model SWMM and the 2D model MOHID Land. The SWMM/Land model is applied to a synthetic street case study and to a real case study in downtown Albufeira, Portugal. The results obtained for the real case study are coherent with local observations of past flooding events, and the model shows potential for better decision-making regarding urban flood risk management.

Illumination guided sparse geometry optimization for target-oriented full-waveform inversion: An ocean bottom node synthetic study

For full-waveform inversion (FWI) with sparse survey layout, it is crucial to optimize the source and receiver geometry toward full-wave illumination. We propose a sparse geometry optimization method and workflow for target-oriented FWI using finite-frequency illumination analysis. The frequency-dependent impact of a source-receiver pair to the wavefield sensitivity kernel and diagonal terms of approximate Hessian matrix are derived under visco-acoustic model assumptions. Based on the reciprocity principle, we use virtual sources in target zone to efficiently calculate the Green's function and illumination from acquisition surface. Optimal locations of sparse receivers are determined by comparing band-limited illumination at reference stations and their surrounding region through an illumination attribute scan. FWI model residual errors are used to evaluate the performance of optimized geometry layout for a given target zone. The performances of different geometries are compared to determine a suitable frequency band for FWI geometry optimization. Synthetic deep water model and ocean bottom node acquisition geometry are used to verify the feasibility of the workflow. Numerical tests in target-oriented FWI show that optimized geometry with constraints of band-limited illumination below10 Hz has better performance than that above 10 Hz. An extension of our geometry optimization method to sparse source configuration is straightforward.

Synthesis and assembly of full-length cyanophage A-4L genome

Artificial cyanophages are considered to be an effective biological method to control harmful cyanobacterial bloom. However, no synthetic cyanophage genome has been constructed and where its obstacles are unclear. Here, we survey a stretch of 16 kb length sequence of cyanophage A-4L that is unclonable in Escherichia coli. We test 12 predicted promoters of cyanophage A-4L which were verified all active in E. coli. Next, we screen for eight ORFs that hindered the assembly of intermediate DNA fragments in E. coli and describe that seven ORFs in the 16 kb sequence could not be separately cloned in E. coli. All of unclonable ORFs in high-copy-number plasmid were successfully cloned using low-copy-number vector, suggesting that these ORFs were copy-number-dependent. We propose a clone strategy abandoned the promotor and the start codon that could be applied for unclonable ORFs. Last, we de novo synthesized and assembled the full-length genome of cyanophage A-4L. This work deepens the understanding of synthetic cyanophages studies.

Synthetic study toward tridachiapyrone B.

A convergent approach to the skeleton of tridachiapyrone B is described taking advantage of the desymmetrization of α,α'-dimethoxy-γ-pyrone leading to α-crotyl-α'-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α'-methoxy-γ-pyrone was applied. The grafting of the simplified target's side chain was demonstrated through an oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α'-methoxy-γ-pyrone motif.

Identification of Nonlinear Soil Properties from Downhole Array Data Using a Bayesian Model Updating Approach.

An accurate seismic response simulation of civil structures requires accounting for the nonlinear soil response behavior. This, in turn, requires understanding the nonlinear material behavior of in situ soils under earthquake excitations. System identification methods applied to data recorded during earthquakes provide an opportunity to identify the nonlinear material properties of in situ soils. In this study, we use a Bayesian inference framework for nonlinear model updating to estimate the nonlinear soil properties from recorded downhole array data. For this purpose, a one-dimensional finite element model of the geotechnical site with nonlinear soil material constitutive model is updated to estimate the parameters of the soil model as well as the input excitations, including incident, bedrock, or within motions. The seismic inversion method is first verified by using several synthetic case studies. It is then validated by using measurements from a centrifuge test and with data recorded at the Lotung experimental site in Taiwan. The site inversion method is then applied to the Benicia-Martinez geotechnical array in California, using the seismic data recorded during the 2014 South Napa earthquake. The results show the promising application of the proposed seismic inversion approach using Bayesian model updating to identify the nonlinear material parameters of in situ soil by using recorded downhole array data.