Chain Substitution Research Articles

Investigation of the Structure-Property Relation of Anthraquinone Dye Molecules with High Dichroism in Guest-Host Liquid Crystal Systems via Computational Methods.

By combining molecular dynamics (MD) simulations and density functional theory (DFT), the influence of dye structure on the optical modulation properties of negative-mode guest-host liquid crystal (GHLC) systems was systematically investigated. Firstly, the reliability of the simulation method was validated by comparing the performance parameters of the GHLC system obtained from simulations with those from experimental results. Subsequently, a series of guest dye molecules, along with their mixtures with negative dielectric anisotropy mesogens, were designed and analyzed. This exploration focused on how variations in dye terminal chain lengths, substitution positions, and substituent group properties affect dye molecular geometry, dye alignment within the host, transition dipole orientation, absorption spectra, and electronic excitation properties. Our findings suggest that dye molecules with a flexible terminal chain substitution of five carbon atoms, positioned at the 2 and 6 locations on the anthraquinone core, exhibit higher order parameters, favorable for enhancing dichroic performance. Moreover, introducing different α-substituents further influences the dye orientation and electronic behavior within the host. These results highlight that structural modifications of anthraquinone-based dyes allow for the design of high-dichroic-ratio materials with customized absorption properties. Overall, our results provide a beneficial understanding of the structure-property relation in GHLC systems, offering valuable guidance for designing high-performance dye molecules and advanced optoelectronic materials in future research.

Методика анализа исполнения бюджета энергосбытовой компании в комбинированных моделях аддитивно-мультипликативного типа

The article presents a methodology developed by the authors for analyzing the budget execution of the power supply company utilizing combined additive-multiplicative models. The relevance of this methodology is underscored by the need for organizations to enhance the effectiveness of management decisions through such analytical frameworks. The novelty of this work lies in the adaptation of classical deterministic analysis models to the specific context of power supply companies, taking into account the peculiarities of their financial and economic activities. A plan-fact analysis of the budget execution of the power supply company was conducted using the chain substitution method, which was implemented across all types of deterministic factor models: additive, multiplicative, multiple, and mixed (combined). This analytical approach enabled the determination of the impact of individual factors on the variation of the performance indicator by gradually substituting the baseline value of each factor indicator within the performance measure with the actual value for the reporting period. The authors conclude that the proposed methodology facilitates the analysis of changes in the performance indicator (marginal profit) attributable to factors of the I, II, III levels. It is applied in practice for the formulation of managerial reporting and the adjustment of the marketing policy of the power supply company operating at the territory of Saint Petersburg.

Dynamic Time-Programming Circuit for Encoding Information, Programming Dissipative Systems, and Delaying Release of Cargo.

Living systems have some of the most sophisticated reaction circuits in the world, realizing many incredibly complex functions through a variety of simple molecular reactions, in which the most notable feature that distinguishes them from artificial molecular reaction networks is the precise control of reaction times and programmable expression. Here, we exploit the hydrolysis-directed nature of λ exonuclease and the programmed responses of the dynamic nanotechnology of nucleic acids to construct a simple, complete, and powerful set of temporally programmed circuits. This system can arbitrarily regulate the degradation rate of the blocker, thereby delaying the nucleic acid chain substitution reaction with less signal leakage. In addition, the powerful dynamic reaction network of nucleic acids enabled us to control the programmed execution of a wide range of reactions in different fields. We have developed a simple strategy to introduce precise control of the time dimension into nucleic acid reaction circuits, which greatly enriches the functionality and applicability of the reaction programs, which can be easily used as timers, compilers, converters, etc. The simplicity, precision, stability, and versatility of such dynamic temporal programming circuits greatly expand the potential of artificial molecular reaction networks for more complex practical applications in biochemistry and molecular biology.

Design, Synthesis and Pro-Inflammatory Activity of Palmitoylated Derivatives of Thioglycolic Acid as New Immunomodulators.

The immune system is essential for the defense against infections and is critically implicated in various disorders, including immunodeficiency, autoimmunity, inflammation and cancer. The current study includes a new design of palmitoylated derivatives of thioglycolic acids (PTGAs) capable of triggering innate immune responses. The new series were accessible through a three-step synthetic route, including N-palmitoylation, Claisen-Schmidt condensation and thia-Michael addition. Their structures were elucidated using different 1D and 2D NMR spectroscopic techniques and their purity was confirmed by elemental analysis. The most active PTGAs induced a 12-26-fold increase in the expression of TNF-α and IL-1β mRNA and triggered a marked release of NO in isolated macrophages. These levels were comparable to the responses elicited by heat-killed E. coli and S. aureus. The position of the palmitamide chain and aryl substitution had a significant effect on the TNF-α and IL-1β mRNA expression and NO release. Simulations of molecular dockings showed that the new PTGA derivatives occupy the same TLR2/TLR6 heterodimer active binding site of the microbial diacylated lipoproteins. The new immunomodulators may have a profound impact on various clinical disorders associated with dysfunctional innate immunity.

Structure-performance relationship and molecular structure optimization design of acid phosphate ester extractants

The extraction performance of acid phosphate ester extractants (PEEs) decreases significantly as the acidity of the aqueous phase increases. Therefore, finding PEEs suitable for high-acid environments has become critical to addressing their performance attenuation. However, the unclear structure-performance relationship of PEEs has led to a lack of guidance in experimental synthesis, significantly impeding the emergence of new acid-resistant PEEs. To tackle these issues, ten novel phenyl phosphate ester extractants were designed based on the molecular formula of phosphodiester (R1R2P(=O)OH) and the conjugation effect of the benzene ring. The relationship between the intrinsic extraction performance of acid PEEs and substituent groups (phenoxy, alkoxy, and alkyl) was quantitatively established by calculating the Gibbs free energy changes of three primary reactions (dimer dissociation, monomer acid ionization, and metal coordination) during divalent cobalt ion extraction. Additionally, the impact of different substitution sites (para, meta, and ortho) of the benzene ring on the extraction performance of acid PEEs was studied. The results indicated that introducing phenoxy groups into traditional acid PEEs (P204 and P507) can effectively enhance the extractants’ acid ionization ability and thermodynamic driving force. The extraction performance of acid PEEs is positively correlated with the number of phenoxy groups, and carbon chain substitution at the meta-position of the benzene ring is the most advantageous. By screening five low-toxicity and low-cost phenolic hydroxyl reagents currently available on the market, design a phenyl phosphate ester extractant ([(CH3)3CCH2C(CH3)2C6H4O]2P(=O)OH, P-4TO) that combines cost and performance advantages. Furthermore, the transition state theory was used to confirm the feasibility of preparing P-4TO, which provided a comprehensive theoretical research method for the future design and synthesis of efficient PEEs.

Spin‐Crossover and Liquid Crystal Property in Fe(II) Complexes: Impact of Alkyl Chain Lengths

AbstractMaterials that combine spin‐crossover (SCO) and liquid crystal (LC) behavior have gained significant attention due to their potential applications in technological devices, attributed to their easy processability. Herein, we report three neutral heteroleptic Fe(II) complexes: [Fe(dpa‐C4)2(NCS)2] (1), [Fe(dpa‐C6)2(NCS)2] (2), and [Fe(dpa‐C16)2(NCS)2] (3) (dpa‐Cn=N‐alkyl‐N‐(pyridin‐2‐yl)pyridin‐2‐amine; n=4, 6 and 16), which exhibit thermal‐induced spin transition behavior. The transition profiles and temperatures are effectively modulated by the length of the alkyl chains. Longer alkyl chains result in gradual and higher T1/2 values, while the shorter chains lead to abrupt SCO with lower T1/2 (i. e. T1/2=259 K (3) >237 K (2) >211 K (1)). Crystallographic studies reveal the impact of hydrophobic and hydrophilic packing in the crystal lattice, contributing to cooperativity and thereby affecting the SCO behavior. Complex 3 with long alkyl chain substitution, displayed non‐synchronized SCO‐LC behavior due to the thermal motion of the alkyl chains.

Bushy-Tailed QACs: The Development of Multicationic Quaternary Ammonium Compounds with a High Degree of Alkyl Chain Substitution.

Quaternary ammonium compounds have served as a first line of protection for human health as surface disinfectants and sanitizers for nearly a century. However, increasing levels of bacterial resistance have spurred the development of novel QAC architectures. In light of the observed reduction in eukaryotic cell toxicity when the alkyl chains on QACs are shorter in nature (≤10 C), we prepared 47 QAC architectures that bear multiple short alkyl chains appended to up to three cationic groups, thus rendering them "bushy-tailed" multiQACs. Antibacterial activity was strong (often ~1-4 μM) in a varied set of bushy-tailed architectures, though observed therapeutic indices were not significantly improved over QAC structures bearing fewer and longer alkyl chains.

An Innovative Method for Deterministic Multifactor Analysis Based on Chain Substitution Averaging

The aims of this paper are to present the methodology, derived mathematical expressions for determining the individual factor influences and the adaptation for the conditions of dynamic deterministic factor analysis and the results of the application of the developed new method for deterministic factor analysis, called the averaged chain substitution method. After formulating the concept of the considered approach, all mathematical expressions used to create models containing up to four factor variables are presented and summarized. The scientific novelty of the study is in the obtained new equations for determining the individual factor influences by the method of averaged chain substitution and the method of analogy for five-factor additive or difference-multiplicative and for five-factor additive or difference-multifactor models with an additive or different part in the numerator of the factor model. The presented mathematical expressions accurately and unambiguously quantify the impact of individual factor influences for all types of factor models and thus significantly expand the applicability of the averaged chain substitution method in the theory and practice of financial-economic analysis. The proposed formalization and algorithmization of the evaluation process makes the method easy to apply by all economic and financial analysts for the purposes of deterministic factor analysis. The methodology was applied to perform a dynamic deterministic factor analysis of the total liquidity of Monbat AD and ELHIM-ISKRA AD for the period 2017–2021, based on the consolidated annual financial statements of the companies, available on the website of the Bulgarian Stock Exchange.

X-Ray-Sensitizers: Organic Pharmaceutical Drug Intermediates Activated Directly by X-Rays to Efficiently Populate Triplet Excitons for Cancer Treatment

Radiotherapy is an important treatment for cancer, but it is associated with major side effects due to the high dose of radiation (generally more than 50 Gy). Because radiation’s low acute and late toxicity, many tumors are treated with fractionated radiation in small doses (< 2 Gy). Scintillator X-ray-induced photodynamic therapy is an efficient methodology for cancer management that employs small doses of X-ray irradiation (< 2 Gy) in a complex process. Here we screened pharmaceutical drug intermediates that are derivatives of thioxanthone (TX) and investigated TX-derived organic pharmaceutical molecules that efficiently undergo X-ray-sensitization to populate triplet excitons (singlet oxygen) for cancer therapy when exposed to low-dose X-ray irradiation. By modifying alkoxy side chain substitutions at the 2-position to tune the molecular packing and intermolecular interactions, the fluorescence and room-temperature phosphorescence of a series of TX derivatives were assessed under X-ray irradiation. The ability of these derivatives to generate singlet oxygen and their potential for treating tumors provide new opportunities for developing organic molecules with simple chemical structures, in which large numbers of triplets can be populated directly under ultralow-dose X-ray irradiation.

Dynamic Determinated Factors Analysis of Labour Productivity in the Bulgarian Energy Subsector

This article presents a dynamic determined factor analysis of labour productivity in the Bulgarian energy subsector for the period 2013 – 2022. The purpose of this article is to reveal the quantitative influences of the factors operating revenues and number of employed persons on the development of the indicator labour productivity in the Bulgarian energy subsector through the averaged chain substitution method. The quantitative influences of operating revenues and number of employed persons on the deviation of the labour productivity indicator in the energy subsector are outlined. The results of the deterministic factor analysis make it possible to draw reasonable conclusions and to reveal the trends in the development of the factors operating revenues and number of employed persons, as well as the indicator of labour productivity in the Bulgarian energy subsector.

Modified Method of Chain Substitutions as an Alternative to the Integral Method of Economic Analysis

The aim is to present the results of the development of a modified method of chain substitutions, which is based on the use of the arithmetic mean sum of the results of the influence of each factor on the indicator of interest, taking into account the priority of each factor in all possible variants. At the same time, from the point of view of accuracy, the results obtained using the modified technique practically do not differ from the results of the integral method, however, they exceed it in terms of using a simpler mathematical apparatus. The relevance of the work is determined by the fact that in modern economic conditions (noticeably increased inflation, problems with energy prices), the issue of applying methods of deterministic factor analysis of expenses and incomes becomes especially significant in order to determine the size of the impact of each factor on a specific economic indicator as accurately as possible. However, the chain substitution method used in the vast majority of cases for deterministic factor analysis is inferior in accuracy to the integral method. The scientific novelty of the work lies in the fact that the author uses strict mathematical proofs of the coincidence of the accuracy of the results of the modified methodology and the integral method for various types of deterministic factor models (additive, multiplicative, multiple), which are supported by real practical calculations. Conclusions: the proposed modified method of chain substitutions, due to its mathematical simplicity and proven accuracy of the results obtained, can be widely used in real practical calculations using methods of economic analysis, especially taking into account the computer implementation of algorithms developed in this technique.

A novel electrochemical biosensor for B-type natriuretic peptide detection based on CRISPR/Cas13a and chain substitution reaction

B-type natriuretic peptide (BNP) is a biomarker for heart failure, a serious and prevalent disease that requires rapid and accurate diagnosis. In this study, we developed a novel electrochemical biosensor for BNP detection based on CRISPR/Cas13a and chain substitution reaction. The biosensor consists of a DNA aptamer that specifically binds to BNP, a T7 RNA polymerase that amplifies the signal, a CRISPR/Cas13a system that cleaves the target RNA, and a two-dimensional DNA nanoprobe that generates an electrochemical signal. The biosensor exhibits high sensitivity, specificity, and stability, with a detection limit of 0.74 aM. The biosensor can also detect BNP in human serum samples with negligible interference, demonstrating its potential for clinical and point-of-care applications. This study presents a novel strategy for integrating CRISPR/Cas13a and chain substitution reaction into biosensor design, offering a versatile and effective platform for biomolecule detection.

Small molecule donor third component incorporating thieno[3,2-b]thiophene unit enables 19.18% efficiency ternary organic solar cells with improved operational stability

The rational design of the third component to enhance the efficiency and stability of organic solar cell (OSC) is a critical and challenge. Herein, a thieno[3,2-b]thiophene (TT) substituted wide-bandgap small molecule donor BTTC, was designed, synthesized and incorporated into the state-of-the-art PM6:L8-BO binary to construct ternary OSC. The rigid side chain and planar molecule skeleton enables strong crystallinity and complementary absorption with binary system. The introduction of BTTC enhanced the molecular packing, fibril-like film and preferred vertical phase separation, yielding balanced and higher charge transport, more efficient exciton dissociation and suppressed charge recombination. Besides, lower energy loss was attained and thus leading to higher open-circuit voltage (VOC). Consequently, the introduction of BTTC achieved the highest efficiency of 18.8% along with extended operational stability. Furthermore, replacing L8-BO to BTP-eC9 further boosted the ternary PCE to 19.18%, standing one of the best charge management in ternary OSC. This work presents efficient rigid side chain substitution strategy to construct the third component of small molecule donor for high performance ternary OSCs with comprehensively improved photovoltaic parameters. This strategy broadens the selection of guest materials toward realizing the actual commercial application of OSCs.

Biochemical Characterization of Rice Xylan Biosynthetic Enzymes in Determining Xylan Chain Elongation and Substitutions.

Grass xylan consists of a linear chain of β-1,4-linked xylosyl residues that often form domains substituted only with either arabinofuranose (Araf) or glucuronic acid (GlcA)/methylglucuronic acid (MeGlcA) residues, and it lacks the unique reducing end tetrasaccharide sequence found in dicot xylan. The mechanism of how grass xylan backbone elongation is initiated and how its distinctive substitution pattern is determined remains elusive. Here, we performed biochemical characterization of rice xylan biosynthetic enzymes, including xylan synthases, glucuronyltransferases and methyltransferases. Activity assays of rice xylan synthases demonstrated that they required short xylooligomers as acceptors for their activities. While rice xylan glucuronyltransferases effectively glucuronidated unsubstituted xylohexaose acceptors, they transferred little GlcA residues onto (Araf)-substituted xylohexaoses and rice xylan 3-O-arabinosyltransferase could not arabinosylate GlcA-substituted xylohexaoses, indicating that their intrinsic biochemical properties may contribute to the distinctive substitution patterns of rice xylan. In addition, we found that rice xylan methyltransferase exhibited a low substrate binding affinity, which may explain the partial GlcA methylation in rice xylan. Furthermore, immunolocalization of xylan in xylem cells of both rice and Arabidopsis showed that it was deposited together with cellulose in secondary walls without forming xylan-rich nanodomains. Together, our findings provide new insights into the biochemical mechanisms underlying xylan backbone elongation and substitutions in grass species.

Spectral Analysis of Injectable Depot Medroxyprogesterone Acetate From the International Market With Diffuse Reflectance Spectrometers: Potential Public Health Implications With Benchtop and Handheld Spectrometers

Depot-medroxyprogesterone acetate (DMPA) is an essential medication used as a form of family planning by millions around the world. Diffuse reflectance spectroscopy (DRS) has a long history as a quality assurance measure for raw ingredient verification in pharmaceutical manufacturing. There are a multitude of DMPA manufacturers in the global marketplace. Prudent supply chain management requires identification of potential suppliers that can be contacted if a current supplier is unavailable. Here, DRS data were collected with benchtop (350–2500 nm) and handheld (900–1700 nm) spectrometers for 16 brands of DMPA. Spectra from sample vials ( N = 262) are compared through principal component analysis and Mahalanobis distances. The benchtop spectrometer proved to be an efficient gauge of the similarities and differences amongst DMPA brands, with subcontracted manufacturers resulting in very similar results to the primary manufacturers. The handheld spectrometer offers advantages in portability and cost and was shown to be an effective brand discrimination tool but was less reliable in the context of identifying potentially suitable supply chain substitution options of DMPA due to several key DMPA spectral features appearing just outside of the handheld spectrometer's range. Data collected from the benchtop spectrometer was used to identify several potential supply chain substitutions, dependent on various other subsequent due-diligence activities (i.e., product documentation reviews and manufacturing site audits). These potential substitutions can be shortlisted for further auditing review prior to being identified as a potential supply chain substitution.

Hydrogen/Deuterium Exchange Mass Spectrometry Provides Insights into the Role of Drosophila Testis-Specific Myosin VI Light Chain AndroCaM.

In Drosophila testis, myosin VI plays a special role, distinct from its motor function, by anchoring components to the unusual actin-based structures (cones) that are required for spermatid individualization. For this, the two calmodulin (CaM) light-chain molecules of myosin VI are replaced by androcam (ACaM), a related protein with 67% identity to CaM. Although ACaM has a similar bi-lobed structure to CaM, with two EF hand-type Ca2+ binding sites per lobe, only one functional Ca2+ binding site operates in the amino-terminus. To understand this light chain substitution, we used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to examine dynamic changes in ACaM and CaM upon Ca2+ binding and interaction with the two CaM binding motifs of myosin VI (insert2 and IQ motif). HDX-MS reveals that binding of Ca2+ to ACaM destabilizes its N-lobe but stabilizes the entire C-lobe, whereas for CaM, Ca2+ binding induces a pattern of alternating stabilization/destabilization throughout. The conformation of this stable holo-C-lobe of ACaM seems to be a "prefigured" version of the conformation adopted by the holo-C-lobe of CaM for binding to insert2 and the IQ motif of myosin VI. Strikingly, the interaction of holo-ACaM with either peptide converts the holo-N-lobe to its Ca2+-free, more stable, form. Thus, ACaM in vivo should bind the myosin VI light chain sites in an apo-N-lobe/holo-C-lobe state that cannot fulfill the Ca2+-related functions of holo-CaM required for myosin VI motor assembly and activity. These findings indicate that inhibition of myosin VI motor activity is a precondition for transition to an anchoring function.

Toxicity of a novel antifungal agent (ATB1651 gel) in Yucatan minipigs (Sus scrofa) following 4weeks of daily dermal administration.

ATB1651 gel is an antifungal drug candidate that enhances antifungal activity through substitution of several aryl rings, alkyl chains, and methyl groups. To ensure safety of use of ATB1651 gel, assessment of its potentially toxic side effects is necessary. In this study, we examined the repeated-dose toxicity of ATB1651 gel to Yucatan minipigs (Sus scrofa) in accordance with the Good Laboratory Practice guidelines. Five doses of ATB1651 gel (0%, 0.2%, 0.5%, 1.0%, 3.0%) were administered dermally to the left and right flanks of 38 minipigs daily for 4weeks. Mortality, clinical symptoms, dermal scores, body weights, and physiological, biochemical, pathological, and toxicokinetic analyses were performed after the treatment period. No systemic toxicological damage was observed in either male or female minipigs regardless of dose; however, dermal application of ATB1651 gel caused some skin alterations at the application sites. Specifically, erythema and eschar formation, edema, and scabs or raise spots were observed at the application site(s) in males in the 3.0% ATB1651 gel treatment group and in females at ATB1651 gel concentrations ≥ 1.0%, with dermal scores ranging from grade 1 to 2. Additionally, histopathological assay indicated infiltration of different types of inflammatory cells and the presence of pustule/crust at the application site(s) in both males and females at ATB1651 gel concentrations ≥ 0.5%. However, these changes were reversible after a 2-week recovery period and were considered a local irritation effect of ATB1651 gel. The no-observed-adverse-effect level of ATB1651 gel was 3.0% with regard to topical and systemic toxicity in both male and female minipigs. Collectively, our results imply that ATB1651 gel is a safe candidate for clinical development as an antifungal drug with a wide therapeutic window.

Permeation of urea and water through sulfonated poly(styrene‐isobutylene‐styrene) membranes with counterion substitution

AbstractThis study describes the influence of counterion substitution on the transport of urea and water through sulfonated poly(styrene‐isobutylene‐styrene) (SIBS) membranes. SIBS was sulfonated to 66.4% to allow for enough ionic domains to transport urea and water through the membrane. Counterions, including alkyl‐substituted ammonium ions, influenced the ionic domains creating a selective barrier that hindered the transport of urea and water through SIBS. Permeability measurements demonstrated that counterion substitution significantly affected the transport of urea. Membranes with higher charge counterions exhibited a more pronounced reduction in permeability due to the formation of crosslinks and increased restriction on molecular diffusion. Membranes substituted with ammonium salts showed reduced permeability due to the alkyl chains' hydrophobic nature, which created a physical barrier against the passage of urea molecules. Pure water flux tests indicated that counterion substitution also reduced the water flux of the membranes. Membranes with +1 counterions showed a small reduction in the water flux, while membranes with higher charge counterions and alkyl chain substitutions exhibited larger reductions, highlighting the influence of crosslinking and hydrophobicity on water transport.

A newly fascinating approach to construct pillar[5]arene functionalized ester derivatives for nematic liquid crystalline behavior

A Pillar[5]arene linked 4-n-alkoxy benzoic acid based multifunctional supramolecular systems ((PB1-PB4) with variable alkyl chains were synthesized and well characterized. The microscopic and thermal behaviors of the compounds were investigated by using POM, DSC, and TGA analysis. All four pillar[5]arene-ester based macrocyclic compounds display nematic type mesomorphic properties, with a well-known schlieren and droplets type texture pattern observed in all four ten-side substituted pillarene derivatives. All four materials exhibit enantiotropic mesogenic behavior with a wide temperature range and thermal stability. The material with higher alkyl chain exhibit nematic phase at lower temperatures compared to materials with lower alkyl chain substitutions. Furthermore, we have investigated the structure property relationship to understand the influence of substitution on the rigid core of pillar[5]arene and its ability to induce different types of liquid crystalline behaviors.

Влияние на фактори върху изменението на брутната печалба и нивото на рентабилност при производство на мляко от синтетична популация Българска млечна

The purpose of the present study is an analysis of the influence of various factors on the indicators of gross profit and level of profitability in the production of milk from sheep of the Bulgarian Dairy Synthetic Population breed for a period of 3 years. Data from the accounting department of Institute of Animal Sciences -Kostinbrod were used. The indicators were analyzed: average yield (l), average selling price of 1 l of milk, cost of variable production costs for 1 l of milk, gross income from milk, gross profit, level of profitability of variable costs. The index factor analysis (method of chain substitution) was used to determine the influence of each factor on the value of the outcome indicator. The absolute change in income (by 31.79%) over the three-year period has an increasing trend. Variable costs are reduced and this has a positive impact on gross profit. In the third year, the reduction in feed cost increases the gross profit. The contribution margin per 1 l of milk has an increasing effect on the level of profitability (by 39.78% and 56.1%) for the second and third years. The level of profitability increased in the third year by 55.65%.