Effect of Residual Water and Microwave Heating on the Half‐Life of the Reagents and Reactive Intermediates in Peptide Synthesis

Precise microwave heating has changed the way many small molecules are being synthesized and, currently, the field of solid‐phase peptide synthesis is undergoing dramatic changes owing to the use of microwave heating. To fully reap the benefits of precise microwave heating for the formation of amide bonds in peptide synthesis, it is important to understand the kinetics of formation and break‐down of activated esters and their N‐acylation of the nascent peptide chain at elevated temperatures. Herein, we present systematic studies of, first, the rate of formation of activated esters by NMR spectroscopy and, second, their N‐acylation during peptide synthesis. A study of the amount of residual water in the solvents revealed a significant effect on electrophilic reagents and intermediates. This observation was expanded into a general study of microwave heating in peptide synthesis.     

ortho‐Phenylenediamine: An Effective Spacer to Build Highly Magnetic Fe3O4/Au Nanocomposites

1,2‐Diaminobenzene, popularly known as ortho‐phenylenediamine (PDA), is found to be a prototype spacer for the deposition of gold nanoparticles on the surfaces of Fe₃O₄ microspheres. Upon carbonization with PDA, the morphology of the product changes significantly, and the resulting nanocomposites exhibit enhanced magnetism beyond the saturation value of Fe₃O₄. The Fe₃O₄/Au nanocomposites show good surface‐enhanced Raman spectroscopy activity with a detection limit of 10^?15 M .     

Preparation and Characterization of Carbon Nano‐Onion/PEDOT:PSS Composites

Composites of unmodified or oxidized carbon nano‐onions (CNOs/ox‐CNOs) with poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are prepared with different compositions. By varying the ratio of PEDOT:PSS relative to CNOs, CNO/PEDOT:PSS composites with various PEDOT:PSS loadings are obtained and the corresponding film properties are studied as a function of the polymer. X‐ray photoelectron spectroscopy characterization is performed for pristine and ox‐CNO samples. The composites are characterized by scanning and transmission electron microscopy and differential scanning calorimetry studies. The electrochemical properties of the nanocomposites are determined and compared. Doping the composites with carbon nanostructures significantly increases their mechanical and electrochemical stabilities. A comparison of the results shows that CNOs dispersed in the polymer matrices increase the capacitance of the CNO/PEDOT:PSS and ox‐CNO/PEDOT:PSS composites.     

Transition‐Metal Complexes of Tetrylones [(CO)5W‐E(PPh3)2] and Tetrylenes [(CO)5W‐NHE] (E=C–Pb): A Theoretical Study

Quantum chemical calculations at the BP86/TZVPP//BP86/SVP level are performed for the tetrylone complexes [W(CO)₅‐E(PPh₃)₂] ( W‐1 E ) and the tetrylene complexes [W(CO)₅‐NHE] ( W‐2 E ) with E=C–Pb. The bonding is analyzed using charge and energy decomposition methods. The carbone ligand C(PPh₃) is bonded head‐on to the metal in W‐1 C , but the tetrylone ligands E(PPh₃)₂ are bonded side‐on in the heavier homologues W‐1 Si to W‐1 Pb . The W? E bond dissociation energies (BDEs) increase from the lighter to the heavier homologues ( W‐1 C : D_e=25.1 kcal mol^?1; W‐1 Pb : D_e=44.6 kcal mol^?1). The W(CO)₅←C(PPh₃)₂ donation in W‐1 C comes from the σ lone‐pair orbital of C(PPh₃)₂, whereas the W(CO)₅←E(PPh₃)₂ donation in the side‐on bonded complexes with E=Si–Pb arises from the π lone‐pair orbital of E(PPh₃)₂ (the HOMO of the free ligand). The π‐HOMO energy level rises continuously for the heavier homologues, and the hybridization has greater p character, making the heavier tetrylones stronger donors than the lighter systems, because tetrylones have two lone‐pair orbitals available for donation. Energy decomposition analysis (EDA) in conjunction with natural orbital for chemical valence (NOCV) suggests that the W? E BDE trend in W‐1 E comes from the increase in W(CO)₅←E(PPh₃)₂ donation and from stronger electrostatic attraction, and that the E(PPh₃)₂ ligands are strong σ‐donors and weak π‐donors. The NHE ligands in the W‐2 E complexes are bonded end‐on for E=C, Si, and Ge, but side‐on for E=Sn and Pb. The W? E BDE trend is opposite to that of the W‐1 E complexes. The NHE ligands are strong σ‐donors and weak π‐acceptors. The observed trend arises because the hybridization of the donor orbital at atom E in W‐2 E has much greater s character than that in W‐1 E , and even increases for heavier atoms, because the tetrylenes have only one lone‐pair orbital available for donation. In addition, the W? E bonds of the heavier systems W‐2 E are strongly polarized toward atom E, so the electrostatic attraction with the tungsten atom is weak. The BDEs calculated for the W? E bonds in W‐1 E , W‐2 E and the less bulky tetrylone complexes [W(CO)₅‐E(PH₃)₂] ( W‐3 E ) show that the effect of bulky ligands may obscure the intrinsic W? E bond strength.     

FMO‐MD Simulations on the Hydration of Formaldehyde in Water Solution with Constraint Dynamics

Full‐quantum mechanical fragment molecular orbital‐based molecular dynamics (FMO‐MD) simulations were applied to the hydration reaction of formaldehyde in water solution under neutral conditions. Two mechanisms, a concerted and a stepwise one, were considered with respect to the nucleophilic addition and the proton transfer. Preliminary molecular orbital calculations by means of polarized continuum model reaction field predicted that the hydration prefers a concerted mechanism. Because the calculated activation barriers were too high for free FMO‐MD simulations to give reactive trajectories spontaneously, a More O’Ferrall–Jencks‐type diagram was constructed from the statistical analysis of the FMO‐MD simulations with constraint dynamics. The diagram showed that the hydration proceeds through a zwitterionic‐like (ZW‐like) structure. The free energy changes along the reaction coordinate calculated by means of the blue moon ensemble for the hydration and the amination of formaldehyde indicated that the hydration proceeds through a concerted process through the ZW‐like structure, whereas the amination goes through a stepwise mechanism with a ZW intermediate. In inspection of the FMO‐MD trajectories, water‐mediated cyclic proton transfers were observed in both reactions on the way from the ZW‐like structure to the product. These proton transfers also have an asynchronous character, in which deprotonation from the nucleophilic oxygen atom (or nitrogen atom for amination) precedes the protonation of the carbonyl oxygen atom. The results showed the strong advantage of the FMO‐MD simulations to obtain detailed information at a molecular level for solution reactions.