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Gram‐positive bacteria represent a significant threat due to their resistance to conventional antibiotics. This study employs computational methods to investigate fusidic acid (FA) derivatives (1–24) as potential antibiotics against Gram‐positive bacteria. Techniques such as density functional theory calculations, molecular docking, and molecular dynamics simulations were utilized to evaluate ligand interactions with target proteins Staphylococcus aureus (S. aureus) elongation factor G (fusA) (2XEX), fusidic acid resistance protein (fusB) (4ADN), and fusidic acid resistance protein (fusC) (2YB5), comparing them to established antibiotics (ceftobiprole, linezolid, vancomycin). Notably, ligand 16 demonstrated a remarkable binding affinity to the S. aureus elongation factor G protein (−8.7 kcal mol⁻¹), closely aligning with both in vitro and in vivo results and outperforming fusidic acid and reference drugs. In silico methods (SwissADME, AdmetSAR, Molinspiration, Molsoft) were used to assess pharmacokinetics and drug‐likeness. Molecular dynamics (MD) simulations confirmed superior S. aureus elongation factor G stability for ligands fusidic acid 1, (Z)‐2‐((3R,4S,8S,9R,10S,11R,13S,14S,16S)‐16‐acetoxy‐3,11‐dihydroxy‐4,8,10,14‐tetramethylhexadecahydro‐17H‐cyclopenta[a]phenanthren‐17‐ylidene)‐5‐cyclohexylidene‐ pentanoic acid (14), (Z)‐2‐((3R,4S,8S,9R,10S,11R,13S, 14S,16S)‐16‐acetoxy‐3,11‐dihydroxy‐4,8,10,14‐tetramethylhexadecahydro‐17H‐cyclopenta[a]phenanthren‐17‐ylidene)‐5cyclohexylidenepentanoic acid (16), and (Z)‐2‐((3R,4S,8S,9R,10S,11R,13S,14S,16S)‐16‐acetoxy‐3,11‐dihydroxy‐4,8,10,14‐tetramethylhexadecahydro‐17H‐cyclopenta[a]phenanthren‐17‐ylidene)‐5‐cyclopentylidenepentanoic acid (17), with ligand 16 exhibiting exceptional stability across various temperatures, especially at human body temperature (310 K). Further molecular dynamics simulations of ligand 16 validated its robust stability and potential to disrupt S. aureus elongation factor G, supporting the docking results and showing strong consistency with in vitro and in vivo findings. Consequently, ligand 16 emerges as a promising candidate for further development as an anti‐Gram‐positive bacterial drug, pending validation through rigorous clinical trials. [ABSTRACT FROM AUTHOR]

Diluting a system with metal complexes can sometimes cause free metal ions to increase in concentration. This paper describes "metal ion anti-buffering", a situation in which free metal ion concentrations rapidly increase as system dilution drives dissociation. It only occurs under excess free ligand conditions when a solution is dominated by higher stoichiometry complexes. The Law of Mass Action is used to provide a mathematical justification for the phenomenon. A Cu[superscript 2+]- ethylenediamine mixture exhibits this phenomenon when excess free ethylenediamine (en) is present. For example, it occurs when diluting a solution containing a 4-fold excess of en over Cu[superscript 2+]. As this mixture is diluted by a factor of 5600, the modeled free Cu[superscript 2+] concentration shows a 470-fold increase. Taken together, this is 2.5 million times higher than dilution of the system would yield in other circumstances. Included are experimental data confirming anti-buffering in the Cu[superscript 2+]-en system. Many other metal-ligand systems can display this behavior. Four additional examples are illustrated, including an amino acid under physiological pH. Anti-buffering TOPOS, a free downloadable Excel workbook, allows readers to simulate this behavior for many metal-ligand systems. A PowerPoint lecture and teaching materials are also provided, suitable for inclusion in upper division and graduate courses in analytical chemistry, biochemistry, and geochemistry.

The rising antimicrobial resistance crisis has diminished the effectiveness of traditional antibiotics against pathogenic bacteria. This study addresses this urgent challenge by exploring the antibacterial potential of novel quinolone derivatives (1–33). Using computational in silico modeling to simulate biological interactions, we aimed to identify candidates with potent antibacterial activity. A total of 33 quinolone derivatives were assessed for their physicochemical properties and effectiveness against a range of clinically relevant pathogens, including methicillin‐resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Streptococcus pneumoniae, and Enterococcus faecalis. Molecular docking studies identified compounds 28, 29, 32, and 33 as having notable binding affinities, particularly against MRSA. Further molecular dynamics simulations of compound 29 confirmed its favorable stability and potential for disrupting MRSA, reinforcing the docking results and showing strong alignment with in vitro findings. These findings position compound 29 as a promising lead for developing alternative MRSA therapies and underscore the need for further in vivo studies to evaluate its therapeutic potential. [ABSTRACT FROM AUTHOR]

"Complexation TOPOS" is a free software package to generate 3-D topographic surfaces ("topos") for metal-ligand complexometric titrations in aqueous media. It constructs surfaces by plotting computed equilibrium parameters above a composition grid with "volume of ligand added" as the x-axis and overall system dilution as the y-axis. The sample systems in this paper are restricted to EDTA as a ligand. Other chelating ligands that form exclusively 1:1 complexes could also be modeled with this software. The surfaces show the quality of the equivalence point break under various conditions. More importantly, they develop the phenomenon of metal ion buffering. They clearly distinguish the difference between "pseudo-buffering" and "true buffering." They introduce terminology for two different forms of metal ion buffering: (1) mass action metal ion buffering under excess ligand conditions and (2) precipitate metal ion buffering when hydroxide precipitates are present under excess metal ion conditions. Systems modeled are EDTA titrations of Cu[superscript 2]+ and Mg[superscript 2+]. Supporting Information for this paper includes the "Complexation TOPOS" software, an Excel workbook that generates topos in under 20 seconds. Required inputs are the following: (1) a stability constant for the metal-ligand complex, (2) acid dissociation constants for the ligand, (3) stability constants for hydroxy complexes of the metal, and (4) a K[subscript sp] value and stoichiometry for hydroxide precipitates. Many constants are tabulated in a workbook tab. Also included are a PowerPoint lecture and teaching materials (for lecture, homework, and prelaboratory activities) that are suitable in general chemistry courses or third-year and graduate courses in analytical chemistry, biochemistry, and geochemistry.

Species TOPOS is a free software package for generating three-dimensional (3-D) topographic surfaces ("topos") for acid-base equilibrium studies. This upgrade adds 3-D species distribution topos to earlier surfaces that showed pH and buffer capacity behavior during titration and dilution procedures. It constructs topos by plotting computed a values above a composition grid with volume of NaOH added as the "x" axis and overall system dilution as the "y" axis. The systematic shift from protonated to deprotonated forms is clearly visualized on a linear "z" axis. Because pH and buffer capacity surfaces accompany the species topos, it is easy to see their interrelationships. On the basis of their graphical appearance, features on species topos have been named corner buttes, corner pits, curving ridge crests, and dilution plains. Ramps connecting surface features are linear when tied to additions of NaOH and logarithmic when associated with the logarithmic dilution axis. The amphiprotic behavior of water is demonstrated by dilution procedures. Systems examined include acetic acid, CH[subscript 3]COOH (a weak monoprotic acid); carbonic acid, H[subscript 2]CO[subscript 3] (a weak diprotic acid), and phosphoric acid, H[subscript 3]PO[subscript 4] (a weak triprotic acid). For comparative purposes, species topos are depicted for a set of three acids with hypothetical pK[subscript a] values of 4.000, 7.000, and 10.000. The Supporting Information includes the Species TOPOS software, macro-enabled spreadsheets that quickly generate pH, buffer capacity, and a surfaces for any mono-, di-, or triprotic acid desired. Only acid dissociation constant (K[subscript a]) values need be changed. Also included are a set of PowerPoint lecture slides and a document entitled "Suggestions on Using Species TOPOS for Teaching" with sections for lecture, worksheet applications, and laboratory activities in first-year college courses and third-year or graduate analytical chemistry courses.

This investigation employed computational methodologies to assess the therapeutic potential of derivatives (1–16) of pyridoxal isonicotinoyl hydrazone (PIH) as potential treatments for tuberculosis. Various computational techniques, including molecular dynamics simulation, molecular docking, density functional theory, and global chemical descriptors, were employed to analyze the interactions between the ligands and target proteins. Docking results indicated that ligands 6, 7, 8, and rifampin exhibited binding affinities of −8.4, −7.4, −9.2, and − 7.2 kcal mol−1, respectively, against mycobacterium tuberculosis enoyl acyl carrier protein reductase (INHA), with ligand 8 demonstrating superior inhibition. Molecular dynamics (MD) simulations were utilized to assess the stability of protein‐ligand interactions. Remarkably, the Root Mean Square Deviation (RMSD) of the INHA‐ligand 8 complex remained minimal, with peak values at.40,.56,.37, and.50 nm at temperatures of 300, 305, 310, and 320 K, respectively. This suggests superior stability compared to the reference drug rifampin and INHA complex, which exhibited an RMSD range of.2 to.8 nm at 300 K. Furthermore, analysis using Frontier Molecular Orbital (FMO) revealed that the Egap value of ligand 8 (4.407 eV) is lower than all the reference drugs except rifampin. This comprehensive theoretical analysis positions ligand 8 as a promising candidate for anti‐tuberculosis drug development, underscoring the need for further exploration through in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

BufCap TOPOS is free software that generates 3-D topographical surfaces ("topos") for acid-base equilibrium studies. It portrays pH and buffer capacity behavior during titration and dilution procedures. Topo surfaces are created by plotting computed pH and buffer capacity values above a composition grid with volume of NaOH as the x axis and overall system dilution as the y axis. What emerge are surface features that correspond to pH and buffer behaviors in aqueous solutions. Topo surfaces are created for pH, log buffer capacity, and linear buffer capacity. Equivalence point breaks become pH cliffs and logarithmic buffer capacity canyons that grow shallower with dilution. Areas of high buffer capacity become rounded ridges. Dilution alone generates 45° ramps. Example systems include hydrochloric acid, HCl (a strong acid); acetic acid, CH[subscript 3]COOH (a weak monoprotic acid); oxalic acid, HOOCCOOH (a weak diprotic acid); and L-glutamic acid hydrochloride, C[subscript 5]H[subscript 9]NO[subscript 4]·HCl (a weak triprotic acid). The Supporting Information includes a copy of the interactive BufCap TOPOS program, macro-enabled spreadsheets that quickly generate surfaces for any mono-, di-, or triprotic acid. Only acid dissociation constants, K[subscript a] values, need be changed. Other materials include teaching slides for lectures, plus worksheets and laboratory activities for first-year college courses and third-year or graduate analytical chemistry courses.

3-D topographic surfaces ("topos") can be generated to visualize how pH behaves during titration and dilution procedures. The surfaces are constructed by plotting computed pH values above a composition grid with volume of base added in one direction and overall system dilution on the other. What emerge are surface features that correspond to behavior in aqueous solutions. Equivalence point breaks become cliffs that pinch out with dilution. Buffer effects become plateaus. Dilution alone generates 45° ramps. Limitations of the Henderson-Hasselbalch equation can be seen by noting the conditions over which a plateau remains relatively flat. Because dissociation is driven by dilution, the surfaces demonstrate when the solution of a weak acid becomes indistinguishable from that of a strong acid. Surfaces are presented for hydrochloric acid, HCl (a strong acid); acetic acid, CH [subscript 3]COOH (a weak monoprotic acid); oxalic acid, HOOCCOOH (a weak diprotic acid) and l-histidine dihydrochloride, C[subscript 6]H[subscript 9]N[subscript 3]O[subscript 2]·2HCl (a weak triprotic acid). Supplementary materials include suggested use of topos in lecture, as worksheets and in support of laboratory activities for first-year college courses and third-year analytical chemistry courses. Also provided is pH TOPOS, the macro-enabled spreadsheets that quickly generate surfaces for any mono-, di-, or triprotic acid desired. Only a change of acid dissociation constants, K[subscript a] values, is required.

Two characteristics of batteries, their delivery of nearly constant voltage and their rapid failure, are explained through a visual examination of the Nernst equation. Two Galvanic cells are described in detail: (1) a wet cell involving iron and copper salts and (2) a mercury oxide dry cell. A complete description of the wet cell requires a three-dimensional Nernst surface because the potential is a function of two variables: the activities of both the oxidized and reduced forms in each redox couple. Dry cell potentials, which utilize solid or pure liquid species, are functions of only one variable and can be described by a pair of traces in a traditional plot. Plots of the Nernst potential are relatively flat for most activities, but they exhibit cliffs under extreme conditions. The flat spots are responsible for the fairly constant voltage that batteries deliver; the cliffs explain why batteries fail so quickly. (Contains 7 figures.)

Fatty acid composition in chicken fast food was analyzed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and gas chromatography-flame ionization detector (GC-FID). Saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) have been found in various amounts in the fast food samples. None of the fast food samples contain trans fatty acid. Chicken Winglet (A) and Chicken Hot Wings (B) have higher amount of saturated fatty acids (SFA) which are 28.73% and 25.92% respectively. The amount of saturated fatty acids (SFA) in Chicken Drumst (C), Chicken Botik (D), Fiery Grilled Chicken (E), Chicken Meatballs (F), and Chicken Nuggets (G) are in between 10.94-19.38%. The saturated fatty acids found in the fast food samples are palmitic acid, stearic acid, and myristic acid. Highest amount of linoleic acid (omega-6, 18.90%) was found in Chicken Meatballs (F). The ratio of omega-6 and omega-3 in sample D was 2.32:1 which is in the acceptable range. Although trans fatty acid was not found in the samples, presence of more than 10% saturated fatty acids in chicken fast food is still harmful for health as it may increase risk of cardiovascular disease (CVD). [ABSTRACT FROM AUTHOR]