Multi‐Species Multi‐Channel (MSMC): An Ab Initio‐based Parallel Thermodynamic and Kinetic Code for Complex Chemical Systems

Multi‐Species Multi‐Channel (MSMC) is an ab initio parallel program to calculate thermodynamic quantities (e.g., , , , and , time‐dependent species profiles, and rate coefficients as functions of temperature and pressure for complex chemical reaction systems, which consist of multiple stable species and multiple reaction channels interconnecting them. Thermodynamic properties of the species involved are calculated using statistical mechanics with molecular information from electronic structure calculations. Temperature‐ and pressure‐dependent behaviors are rigorously characterized within the eigenpair master equation/Rice–Ramsperger–Kassel–Marcus (ME/RRKM) framework. Corrections, e.g., for hindered internal rotation and tunneling treatment, are included. With the implementation of an ultra‐high precision package and rigorous matrix setup, MSMC is able to correctly mimic real behaviors of different types of chemical systems. Different eigenpair‐based approaches to extract phenomenological/macroscopic rate coefficients are implemented for different applications. Moreover, a friendly and platform‐independent graphical‐user‐interface (GUI) is provided to facilitate the use of MSMC and the pre‐/postcalculation data visualization/analysis on the fly. The program can be freely downloaded at https://sites.google.com/site/msmccode/ .     

Structural Factors and Mechanisms Underlying the Improved Photodynamic Cell Killing with Silicon Phthalocyanine Photosensitizers Directed to Lysosomes Versus Mitochondria

The phthalocyanine photosensitizer Pc 4 has been shown to bind preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, especially Bcl-2, are photodamaged and apoptosis, as indicated by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase, is triggered. A series of analogs of Pc 4 were synthesized, and the results demonstrate that Pcs with the aminopropylsiloxy ligand of Pc 4 or a similar one on one side of the Pc ring and a second large axial ligand on the other side of the ring have unexpected properties, including enhanced cell uptake, greater monomerization resulting in greater intracellular fluorescence and three-fold higher affinity constants for liposomes. The hydroxyl-bearing axial ligands tend to reduce aggregation of the Pc and direct it to lysosomes, resulting in four to six times more killing of cells, as defined by loss of clonogenicity, than with Pc 4. Whereas Pc 4-PDT photodamages Bcl-2 and Bcl-xL, Pc 181-PDT causes much less photodamage to Bcl-2 over the same dose–response range relative to cell killing, with earlier cleavage of Bid and slower caspase-3-dependent apoptosis. Therefore, within this series of photosensitizers, these hydroxyl-bearing axial ligands are less aggregated than is Pc 4, tend to localize to lysosomes and are more effective in overall cell killing than is Pc 4, but induce apoptosis more slowly and by a modified pathway.     

Determination of sugar structures in solution from residual dipolar coupling constants: methodology and application to methyl beta-D-xylopyranoside

We have developed methodology for the determination of solution structures of small molecules from residual dipolar coupling constants measured in dilute liquid crystals. The power of the new technique is demonstrated by the determination of the structure of methyl beta-d-xylopyranoside (I) in solution. An oriented sample of I was prepared using a mixture of C(12)E(5) and hexanol in D(2)O. Thirty residual dipolar coupling constants, ranging from -6.44 to 4.99 Hz, were measured using intensity-based J-modulated NMR techniques. These include 15 D(HH), 4 (1)D(CH), and 11 (n)D(CH) coupling constants. The accuracy of the dipolar coupling constants is estimated to be < +/- 0.02 Hz. New constant-time HMBC NMR experiments were developed for the measurement of (n)D(CH) coupling constants, the use of which was crucial for the successful structure determination of I, as they allowed us to increase the number of fitted parameters. The structure of I was refined using a model in which the directly bonded interatom distances were fixed at their ab initio values, while 16 geometrical and 5 order parameters were optimized. These included 2 CCC and 6 CCH angles, and 2 CCCC and 6 CCCH dihedral angles. Vibrationally averaged dipolar coupling constants were used during the refinement. The refined solution structure of I is very similar to that obtained by ab initio calculations, with 11 bond and dihedral angles differing by 0.8 degrees or less and the remaining 5 parameters differing by up to 3.3 degrees . Comparison with the neutron diffraction structure showed larger differences attributable to crystal packing effects. Reducing the degree of order by using dilute liquid crystalline media in combination with precise measurement of small residual dipolar coupling constants, as shown here, is a way of overcoming the limitation of strongly orienting liquid crystals associated with the complexity of (1)H NMR spectra for molecules with more than 12 protons.     

Probing the transition from hydrophilic to hydrophobic solvation with atomic scale resolution

Picosecond and femtosecond X-ray absorption spectroscopy is used to probe the changes of the solvent shell structure upon electron abstraction of aqueous iodide using an ultrashort laser pulse. The transient L(1,3) edge EXAFS at 50 ps time delay points to the formation of an expanded water cavity around the iodine atom, in good agreement with classical and quantum mechanical/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. These also show that while the hydrogen atoms pointed toward iodide, they predominantly point toward the bulk solvent in the case of iodine, suggesting a hydrophobic behavior. This is further confirmed by quantum chemical (QC) calculations of I(-)/I(0)(H(2)O)(n=1-4) clusters. The L(1) edge sub-picosecond spectra point to the existence of a transient species that is not present at 50 ps. The QC calculations and the QM/MM MD simulations identify this transient species as an I(0)(OH(2)) complex inside the cavity. The simulations show that upon electron abstraction most of the water molecules move away from iodine, while one comes closer to form the complex that lives for 3-4 ps. This time is governed by the reorganization of the main solvation shell, basically the time it takes for the water molecules to reform an H-bond network. Only then is the interaction with the solvation shell strong enough to pull the water molecule of the complex toward the bulk solvent. Overall, much of the behavior at early times is determined by the reorientational dynamics of water molecules and the formation of a complete network of hydrogen bonded molecules in the first solvation shell.     

Carbaborane‐Substituted 1,2,3‐Triphospholanes and 1‐Aza‐2,5‐diphospholane: New Synthetic Approaches

New phosphorus‐containing, five‐membered P,P,P and P,N,P heterocycles were synthesized and fully characterized. The P,P,P heterocycles, 1,2,3‐triphospholanes, can be synthesized by two different facile pathways, whereas the P,N,P compound, a 1‐aza‐2,5‐diphospholane, can only be obtained with silylamine.     

From Enantiopure Hydroxyaldehydes to Complex Heterocyclic Scaffolds: Development of Domino Petasis/Diels–Alder and Cross‐Metathesis/Michael Addition Reactions

One‐step assembly of hexahydroisoindole scaffolds by a sequence that combines the Petasis (borono‐Mannich) and Diels–Alder reactions is described. The unique selectivity observed experimentally was confirmed by quantum calculations. The current method is applicable to a broad range of substrates, including free sugars, and holds significant potential to efficiently and stereoselectively build new heterocyclic structures. This easy and fast entry to functionalized polycyclic compounds can be pursued by further transformations, for example, additional ring closure by a cross‐metathesis/Michael addition domino sequence.     

Decarboxylative cross-couplings of 2-aminopyrimidine-5-carboxylic acids

Decarboxylative CC cross-couplings of 2-aminopyrimidine-5-carboxylic acids under a Pd/Ag-based catalytic system opens a new platform for the introduction of diverse C5 substituents. The reaction methods proceeded efficiently with a wide range of the acids and the coupling partners of aryl iodides, alkenes, bromoalkynes, and azoles. Considering ready availability of 2-aminopyrimidine-5-carboxylic acid from the oxidative dehydrosulfurative CN cross-coupling of the 3,4-dihydropyrimidin-1H-2-thiones, this reaction method unambiguously pave a shortcut to densely substituted 2-aminopyrimidine derivatives with unprecedented diversity.     

Thermodynamics of the formation of Cu<Superscript>2+</Superscript>–glycyl-glycyl-glycine complex in water–ethanol solutions at 298 K

The stability constants of monoligand complexes of copper(II) ions with glycyl-glycyl-glycine zwitterions (triglycine, HL^±) and triglycinate ions (L^?) in a water–ethanol solvent with 0.0, 0.1, 0.3, and 0.5 mole fractions of ethanol at an ionic strength of 0.1 created by sodium perchlorate and temperature Т = 298.15 K are determined by means of potentiometric titration. It is found that an increase of ethanol content improves the stability of the investigated complexes, due mainly to the resolvation of ligands.     

Analysis of trace elements in the fingernails of breast cancer patients using instrumental neutron activation analysis

Journal of Radioanalytical and Nuclear Chemistry - The aim of this study was to find trace elements that increase risk of breast cancer based on the deviation of the concentration of trace elements...     

Synthesis and Transformation of 4-(1-Chloro-1-nitroethyl)-6,7-dimethoxy-2-methylquinazoline: Spectral Characterization and Anti-cancer Properties of some Novel Quinazoline Derivatives

An efficient and simple method has been reported for the synthesis of 4-(1-Chloro-1-nitroethyl)-6,7-dimethoxy-2-methylquinazoline ( 2 ) as a key compound for further transformation to other novel 6,7-dimethoxy-2-methyl-4-substituted quinazolines. The structure of the synthesized compounds was characterized by spectroscopic methods. The pathway of some unprecedented reactions was proposed. (E)-1-(6,7-dimethoxy-2-methylquinazolin-4-yl)-3-(4-nitrophenyl)prop-2-en-1-one (11) exhibits high in vitro cytotoxicity on three cell lines, Hepatocellular carcinoma (Hep-G2), Human lung carcinoma (LU-1), and Human breast carcinoma (MCF-7) with IC₅₀ of 2.1, 11.6 and 2.2 μM, respectively.