The structural characteristics of organozinc complexes incorporating N,N'-bidentate ligands

Dimethylzinc reacts with an excess of N-2-pyridylaniline 6 to give the homoleptic species, Zn[PhN(2-C(5)H(4)N)](2) 8. Single crystal X-ray diffraction reveals a solid-state dimer based on an 8-membered (NCNZn)(2) core motif. Zn[CyN(2-C(5)H(4)N)]Me (Cy =c-C(6)H(11)) 10, prepared by the combination of ZnMe(2) with the corresponding cyclohexyl-substituted pyridylamine, is also dimeric in the solid state but reveals a central (ZnN)(2) metallacycle. Employment of (p-Tol)NH(2-C(5)H(4)N)(p-Tol = 4-MeC(6)H(4)) 11 yielded the tris(zinc) adduct Zn(3)[(p-Tol)N(2-C(5)H(4)N)](4)Me(2) 12, which incorporates a central chiral molecule of 'Zn[(p-Tol)N(2-C(5)H(4)N)](2)' 12a, that bridges two 'Zn[(p-Tol)N(2-C(5)H(4)N)]Me' 12b units. A similar trimetallic structure is noted when the pyridylaniline substrate 11 is replaced with the bicyclic guanidine 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH), affording Zn(3)(hpp)(4)Me(2) 13. Spectroscopic studies point to retention of the solid-state structure of in hydrocarbon solution. Reaction of 13 with dimesityl borinic acid, Mes(2)BOH (Mes = mesityl), affords Zn(3)(hpp)(4)(OBMes(2))(2) 14 in which the trimetallic core is retained. This reactivity is in contrast to the closely related reaction of dimeric Zn[Me(2)NC[N(i)Pr](2)]Me 15 with Mes(2)BOH, which yielded Zn[Me(2)NC[N(i)Pr](2)][OBMes(2)].Me(2)NC[N(i)Pr][NH(i)Pr] 16 as a result of protonation at the guanidine ligand in addition to the Zn-Me bond.     

BonDNet: a graph neural network for the prediction of bond dissociation energies for charged molecules

A broad collection of technologies, including e.g. drug metabolism, biofuel combustion, photochemical decontamination of water, and interfacial passivation in energy production/storage systems rely on chemical processes that involve bond-breaking molecular reactions. In this context, a fundamental thermodynamic property of interest is the bond dissociation energy (BDE) which measures the strength of a chemical bond. Fast and accurate prediction of BDEs for arbitrary molecules would lay the groundwork for data-driven projections of complex reaction cascades and hence a deeper understanding of these critical chemical processes and, ultimately, how to reverse design them. In this paper, we propose a chemically inspired graph neural network machine learning model, BonDNet, for the rapid and accurate prediction of BDEs. BonDNet maps the difference between the molecular representations of the reactants and products to the reaction BDE. Because of the use of this difference representation and the introduction of global features, including molecular charge, it is the first machine learning model capable of predicting both homolytic and heterolytic BDEs for molecules of any charge. To test the model, we have constructed a dataset of both homolytic and heterolytic BDEs for neutral and charged (−1 and +1) molecules. BonDNet achieves a mean absolute error (MAE) of 0.022 eV for unseen test data, significantly below chemical accuracy (0.043 eV). Besides the ability to handle complex bond dissociation reactions that no previous model could consider, BonDNet distinguishes itself even in only predicting homolytic BDEs for neutral molecules; it achieves an MAE of 0.020 eV on the PubChem BDE dataset, a 20% improvement over the previous best performing model. We gain additional insight into the model''s predictions by analyzing the patterns in the features representing the molecules and the bond dissociation reactions, which are qualitatively consistent with chemical rules and intuition. BonDNet is just one application of our general approach to representing and learning chemical reactivity, and it could be easily extended to the prediction of other reaction properties in the future.

Prediction of bond dissociation energies for charged molecules with a graph neural network enabled by global molecular features and reaction difference features between products and reactants.     

Polarizing a hydrophobic cavity for the efficient binding of organic guests: the case of calix[6]tren, a highly efficient and versatile receptor for neutral or cationic species

The host-guest properties of calix[6]tren 1 have been evaluated. The receptor is based on a calix[6]arene that is covalently capped at the narrow rim by a tren unit. As a result, the system presents a concave hydrophobic cavity with, at its bottom, a grid-like nitrogenous core. Despite its well-defined cavity and opening to the outside at the large rim, 1 did not behave as a good receptor for neutral molecules in chloroform. However, it exhibited efficient endo-complexation of ammonium guests. By contrast, the per-protonated host, 1.4H(+), behaved as a remarkable receptor for small organic molecules. The complexation is driven by a strong charge-dipole interaction and hydrogen bonds between the polar guest and the tetracationic cap of the calixarene. Finally, coordination of Zn(2+) to the tren core led to the asymmetrization of calixarene cavity and to the strong but selective endo-binding of neutral ligands. This study emphasizes the efficiency of a receptor presenting a concave hydrophobic cavity that is polarized at its bottom. The resulting combination of charge-dipole, hydrogen bonding, CH-pi, and van der Waals interactions highly stabilizes the supramolecular architectures. Also, importantly, the tren cap allows the tuning of the polarization, offering either a basic (1), a highly charged and acidic (1.4H(+)), or a coordination (1.Zn(2+)) site. As a result, the system proved to be highly versatile, tunable, and interconvertible in solution by simple addition of protons, bases, or metal ions.     

Method Development for the Speciation of Chromium in River and Industrial Wastewater Using GFAAS

A simple, sensitive and inexpensive method for the speciation of Cr(VI) and Cr(III) in river and industrial wastewater was developed, optimized and validated. Samples were collected, filtered and then chromium species were determined in the filtrate. In the filtrate, total Cr was determined directly by Graphite Furnace Atomic Absorption Spectrometry (GFAAS). A portion of the filtered sample was buffered to pH 6.4, extracted with Amberlite LA-2/MIBK and finally Cr(VI) was determined in the organic extract and Cr(III) in the aqueous phase using GFAAS. The method was evaluated by analysis of the certified reference material, CRM 544, and good accuracy was obtained. The limit of detection for Cr(VI) and Cr(tot)/Cr(III) was found to be 0.30 and 0.08 µg L⁻¹, respectively, and a precision expressed as relative standard deviation of better than 11% was achieved for nine replicates. A number of water samples from the Tinishu Akaki River, Ethiopia, and wastewater samples from a chemical plant in Germany, were analysed. In addition to the GFAAS method, Cr(tot) was also determined using ICP-MS (in CRM 544, lyophilized water, and Tinishu Akaki River water samples) and Cr(tot) and Cr(VI) using UV-VIS spectrophotometry (in CRM 544 and industrial wastewater samples). Good agreement between the different methods was found.     

Toward fully synthetic carbohydrate-based HIV antigen design: on the critical role of bivalency

Synthetic gp120331-335 glycopeptide fragments carrying hybrid and high-mannose type N-linked glycans were evaluated for binding to broadly neutralizing antibody 2G12 using surface plasmon resonance technology. None of the hybrid-type constructs demonstrated binding to 2G12. In the high-mannose series, the "Cys dimer" construct, presenting two undecasaccharide glycans, showed significantly higher binding than the Cys-protected monomer. The binding of the dimeric structure was further investigated in competition with recombinant gp120. The data suggest that gp120 and its designed synthetic epitope construct bind to the same site on 2G12.     

Nucleotide/Protein Interaction: Energetic and Structural Features of Na,K-ATPase

Microcalorimetric titrations allow to recognize and investigate high-affinity ligand binding to Na,K-ATPase. Titrations with the cardiac glycoside Ouabain, which acts as a specific inhibitor of the enzyme, have provided not only the thermodynamic parameters of high-affinity binding with a stoichiometric coefficient of about 0.6 but also evidence for low-affinity binding to the lipid. The marked enthalpic contribution of -95 kJ mol^-1 at 298.2 K is partially compensated by a large negative entropy change, attributed to an increased interaction between water and the protein. The calorimetric ADP and ATP titrations at 298.2 K are indicative of high-affinity nucleotide binding either in 3 mM NaCl, 3 mM MgCl₂ or at high ionic strength such as 120 mM choline chloride. However, no binding is detected in the buffer solution alone at low ionic strength. The affinities for ADP and ATP are similar, around 10⁶ M^-1 and the stoichiometric coefficients are close to that of Ouabain binding. The exothermic binding of ADP is characterized by a ΔH and ΔS value of -65 kJ mol^-1 and -100 J mol^-1 K^-1, respectively. TheΔH value for ATP binding is larger than for ADP and is compensated by a larger, unfavorable ΔS value. This leads to an enthalpy/entropy compensation, which could express that H-bond formation represents the major type of interaction. As for Ouabain, the negative ΔS values that are also characteristic of nucleotide binding can indicate an increase of solvate interaction with the protein due to a conformational transition occurring subsequent to the binding process. The resulting binding constants are discussed with regard to the results of other studies employing different techniques. A molecular interaction model for nucleotide binding is suggested. This revised version was published online in July 2006 with corrections to the Cover Date.     

3-Deaza-2′-deoxyadenosine: Synthesis via 4-(methylthio)-1H-imidazo[4,5-c]pyridine 2′-deoxyribonucleosides and properties of oligonucleotides

The synthesis of 4-(methylthio)-1H-imidazo[4,5-c]pyridine 2′-deoxy-β-D -ribonucleosides 2 and 9 and the conversion of the N¹-isomer 2 into the 2′,3′-didehydro-2′,3′-dideoxyribonucleoside 3a or (via 7 ) 3-deaza-2′-deoxyadenosine ( 1 ) is described. Phosphonate building blocks of 1 were employed in solid-phase synthesis of self-complementary base-modified oligonucleotides. Their properties were studied with regard to duplex stability and hydrolysis by the restriction enzyme Eco RI.     

Epitope promiscuity of human monoclonal autoantibodies to T-cell receptor-combining site determinants

To characterize the binding specificity and light- and heavy-chain variable region usage in monoclonal human autoantibodies (mAAbs) to T-cell receptors, we constructed heterohybridomas from peripheral blood B cells of three rheumatoid arthritis (RA) patients. From a panel of more than 200 heterohybridomas secreting IgM autoantibodies binding to T-cell receptor Vbeta chain first complementarity determining segments (CDR1), we characterized two IgM/lambda molecules from a single patient in detail. These bound to both CDR1 peptide epitopes and intact TCR of recombinant single-chain T-cell receptor constructs, and to T-cell surface TCR. Spectratype analysis using epitopes mimicking a set of 24 Vbeta genes indicated that one molecule bound only a few members of the set, whereas the second showed considerable epitope promiscuity by binding to more than half of the tested CDR1 peptides. Both mAAbs used variants of a Vlambda3 gene that were very similar to one another and to the germline gene. The epitope-promiscuous autoantibody used a V(H)4 gene identical to a germline prototype, while the other incorporated a V(H)3 sequence differing in only a single residue from its germline prototype. The CDR3s of both were large and distinct from each other as well as from the corresponding segments of rheumatoid factors and "cold agglutinins" using the same or related V(H) germline genes. These mAAbs offer models for deciphering the basis of epitope promiscuity, and serve as candidates for direct use in immunomodulation because they are of intrinsic human origin and do not require molecular engineering to adapt them for use in therapy.     

Polymerization studies on allylic compounds. III. α(substituted methyl)styrenes

The free-radical polymerization of a series of α-(substituted methyl)styrenes was investigated. These compounds were found to be inactive in homopolymerizations but copolymerized with methyl methacrylate and styrene with a retarding effect. Copolymerization characteristics were followed by rate and viscosity measurements.     

Laser ablation in analytical chemistry-a review

Laser ablation is becoming a dominant technology for direct solid sampling in analytical chemistry. Laser ablation refers to the process in which an intense burst of energy delivered by a short laser pulse is used to sample (remove a portion of) a material. The advantages of laser ablation chemical analysis include direct characterization of solids, no chemical procedures for dissolution, reduced risk of contamination or sample loss, analysis of very small samples not separable for solution analysis, and determination of spatial distributions of elemental composition. This review describes recent research to understand and utilize laser ablation for direct solid sampling, with emphasis on sample introduction to an inductively coupled plasma (ICP). Current research related to contemporary experimental systems, calibration and optimization, and fractionation is discussed, with a summary of applications in several areas.