Kinetics and mechanisms of hydrolysis of tetraphenylporphyrins tethered to silicate glass via a primary or tertiary alcohol linker

Tetraphenylporphyrins carrying primary or tertiary alcohols in a phenyl group were bonded to silicate glass by heat treatment. The rate of base catalyzed hydrolysis of tertiary ester was 20 times slower than that of primary ester, while the rate of acid catalyzed hydrolysis of tertiary ester was only 2.5 times slower than that of primary ester. Hydrolysis of tertiary alcohol bonded silica in HCl/H₂¹⁸O${{\text{H}}_2}^{18}\text{O}$ displayed that there is a covalent bond between alcohol oxygen and silicon, and the C–O bond is cleaved under acidic conditions, while the Si–O bond is cleaved under basic conditions.     

Kinetic and mechanistic studies of the hydrolysis of sulfamate esters: a non-elimination decomposition route

The kinetics of hydrolysis at pH 2 and ionic strength (μ) = 1 of a series of sulfamate esters p-XC₆H₄OSO₂NH₂ have been examined using structure- and solvent-reactivity studies, thermodynamic data, a ‘nucleophilicity test’ and a kinetic solvent isotope effect to probe the mechanism of the hydrolysis. These esters can be regarded as models for the more complex medicinally and biologically important esters now under extensive study. The mechanism of hydrolysis involves the neutral ester undergoing nucleophilic attack by water in a bimolecular TS.     

Hydrolysis of esters of certain substitutes of 1,3,5-triazine

The mechanism of hydrolysis of esters of triazine substitutes was studied. It was shown that hydrolysis of l-menthyl esters in both alkaline and acid media at 80–120° C takes place with cleavage of the bond between the oxygen and carbon of triazine. The bond between the oxygen and carbon of alcohol is broken at 180–200° C in acid medium. The kinetics of alkaline hydrolysis of triazine esters was studied, and it was established that the stability of the latter increases in relation to the influence of the substitute in triazine in the order: C₆H₅ < NHC₆H₅ < NHC₂H₅ < N(C₂H₅)₂. A number of new C-substitutes of triazine was synthesized.We thank Prof. A. I. Korolev for the proposal, and the attention he gave to this work.     

Synthesis of carboxylic acids based on the closo-decaborate anion

A series of new boron-containing carboxylic acids was prepared by the ring-opening reaction of cyclic oxonium derivatives of the closo-decaborate anion [B₁₀H₁₀]²⁻ with methyl esters of hydroxybenzoic acids or the cyanide anion followed by hydrolysis of the obtained nitrile and esters. Acid hydrolysis of the esters results in protonation of the oxygen atom connected to the boron cage, with the formation of the corresponding O-protonated acids, isolated in the solid state. The compounds synthesized can be used in radionuclide diagnostics and boron neutron capture therapy of cancer.     

SIFT studies of the reactions of H3O+, NO+ and O+2 with a series of volatile carboxylic acids and esters

We report the results of a selected ion flow tube (SIFT) study of the reactions of H₃O⁺, NO⁺ and O⁺₂ with some nine carboxylic acids and eight esters. We assume that all the exothermic proton transfer reactions of H₃O⁺ with all the acid and esters molecules occur at the collisional rate, i.e. the rate coefficients, k, are equal to k_c; then it is seen that k values for most of the NO⁺ and O⁺₂ reactions also are equal to or close to k_c. The major ionic products of the H₃O⁺ reactions with both the acids and esters are the protonated parent molecules, MH⁺, but minor channels are also evident, these being the result of H₂O elimination from the excited (MH⁺)1 in some of the acid reactions and an alcohol molecule elimination (CH₃OH or C₂H₅OH) in some of the ester reactions. The NO⁺ reactions with the acids and esters result in both ion-molecule association producing NO⁺M in parallel with hydroxide ion (OH⁻) transfer with some of the acids, and parallel methoxide ion (CH₃O⁻) and ethoxide ion (C₂H₅O⁻) transfer as appropriate with some of the esters. The O⁺₂ reactions proceed by dissociative charge transfer with the production of two or more ionic fragments of the parent molecules, the different isomeric forms of both the acid and the ester molecules resulting in different product ions.     

Selective Hydrolysis of Terminal Glycosidic Bond in α-1-Acid Glycoprotein Promoted by Keggin and Wells–Dawson Type Heteropolyacids

The reactivity of a range of Keggin and Wells–Dawson type heteropolyacids (HPAs): H₃PW₁₂O₄₀ H₄SiW₁₂O₄₀, H₃PMo₁₂O₄₀, K₆P₂W₁₈O₆₂, and NaH₂W₁₂O₄, towards the heavily glycosylated α-1-acid glycoprotein (AGP) is reported. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) show that after incubation of the protein with HPAs at 80 °C and pH 2.8 complete hydrolysis of terminal glycosidic bond has been achieved, resulting in the removal of sialic acids with no observed destruction of the protein core or the residual glycan chains. The ¹H NMR spectroscopy confirmed that the released sialic acids preserve intact structure upon their excision from the protein, which makes the reported method suitable for the analysis of sialic acid modifications which play an important role in numerous biological processes. The presence of other sugars was not detected by ¹H NMR and HPAEC-PAD, suggesting that HPAs hydrolyze only the terminal glycosidic bond in the glycoprotein, resulting in the selective release of sialic acid from AGP. The kinetic results have shown that under equal temperature and pH conditions, the hydrolysis of the terminal glucosidic bond occurred faster in the presence of HPAs compared to conventional mineral acids. The observed rate constants were in the range 6,7×10⁻² −11,9×10⁻² min⁻¹ and the complete and selective excision of sialic acids could be achieved within 60 min of incubation. The Trp fluorescence and CD spectroscopy show that non-covalent interaction between HPA and protein takes place in solution which could lead to stabilization of the sialosyl cation that is formed during the glycosidic bond hydrolysis by anionic HPA cluster.     

Hydrolysis of new phthalimide-derived esters catalyzed by immobilized lipase

The last step of the production of four phthalimide-derived acids, designed to act as antiasthma drugs, was performed by enzymatic hydrolysis of the respective methyl or ethyl esters. The esters 4-ethyl-[2-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)]-phenoxyacetic methyl ester (PHT-MET), 4-ethyl-[2-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)]-phenoxyacetic ethyl ester, 4-(1,3-dioxo-1,3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester, and 2-(1,3-dioxo-1, 3-dihydro-2-isoindoylyl)-phenoxyacetic ethyl ester were hydrolyzed by immobilized lipase. The enzymatic reaction could be used only to produce the desired 4-substituted compounds. The best result that was found to hydrolysis of PHT-MET, and, therefore, that ester was selected for optimization experiments in a three-phase system. Reactions were performed with solid biocatalyst (Lipozyme® RM IM), organic solvent phase (ethyl acetate), and aqueous phase (saturated Na₂CO₃ solution). To optimize the reaction conditions, an experimental design optimization procedure was used. The variables studied were the amount of enzyme, the temperature, and the volume of the aqueous solution. Time course experiments were then performed for different initial enzyme concentrations (0.5, 0.9, and 1.4 U_H/mL of solvent). The optimized reaction conditions found were 20 mg of Lipozyme (0.9 U_H/mL_solvent) and 5.0 mL of Na₂CO_3(sat) at 40°C for 6 h.     

Detection of NO2 by hexa-peri-hexabenzocoronene nanographene: A DFT study

It has been previously indicated that pristine graphene cannot detect NO₂ gas. Nanographene is a segment of graphene whose end atoms are saturated with hydrogen atoms and its properties are different from those of graphene. Herein, we investigated the reactivity, electronic sensitivity, and structural properties of hexa-peri-hexabenzocoronene (HBC) nanographene toward NO₂ gas using density functional theory calculations. It was found that the central and peripheral rings of HBC are aromatic but the middle rings are non-aromatic, following Clar's sextet rule of aromaticity. The NO₂ molecule prefers to be adsorbed on the central ring with a nitro configuration, releasing an energy of about 13.2 kJ/mol. The NO₂ molecule significantly stabilizes the LUMO level of the HBC, thereby reducing the HOMO–LUMO energy gap from 3.60 to 1.35 eV. This indicates that the HBC is converted from a semiconductor to a semimetal. It was shown that the adsorption of NO₂ gas by HBC can produce an electrical signal selectively in the presence of O₂, H₂, N₂, CO₂, and H₂O gases. A short recovery time about 1.9 ns is predicted and the effect of density functional is investigated.     

Synthesis of C-11 linked active ester derivatives of vitamin D3 and their conjugations to 42-residue helix-loop-helix peptides

Derivatives of vitamin D₃ carrying an 8-carbon linker at C-11 terminating in an active ester were synthesized from commercial vitamin D₃ using a disassembly-reassembly strategy. Vitamin D₃ was cleaved at the C6-C7 double bond and the ‘upper’ fragment was converted, via a series of reactions, to derivatives substituted at C-11 with an 8-carbon linker terminating in an ethyl ester. Reassembly with modified ‘lower’ fragments using Horner-Wittig olefination followed by linker ester hydrolysis and re-esterification with p-nitrophenol gave C-11 substituted p-nitrophenyl esters. These vitamin D derivatives were conjugated to 42-amino acid helix-loop-helix peptides by reaction of their p-nitrophenyl esters with lysyl side-chain amino groups on the peptides. The vitamin D—peptide conjugates, being potential specific binder candidates for vitamin D-binding protein, were characterized by mass spectroscopy and CD measurements.     

Controlled Release of Perfumery Alcohols by Neighboring‐Group Participation. Comparison of the Rate Constants for the Alkaline Hydrolysis of 2‐Acyl‐, 2‐(Hydroxymethyl)‐, and 2‐Carbamoylbenzoates

A series of 2‐acylbenzoates 1 and 2 , 2‐(hydroxymethyl)benzoates 3 , 2‐carbamoylbenzoates 4 – 6 , as well as the carbamoyl esters 7 or 8 of maleate or succinate, respectively (see Fig. 2), were prepared in a few reaction steps, and the potential use of these compounds as chemical delivery systems for the controlled release of primary, secondary, and tertiary fragrance alcohols was investigated. The rate constants for the neighboring‐group‐assisted alkaline ester hydrolysis were determined by anal. HPLC in buffered H₂O/MeCN solution at different pH (Table 1). The rates of hydrolysis were found to depend on the structure of the alcohol, together with the precursor skeleton and the structure of the neighboring nucleophile that attacks the ester function. Primary alcohols were released more rapidly than secondary and tertiary alcohols, and benzoates of allylic primary alcohols (e.g., geraniol) were hydrolyzed 2–4 times faster than their homologous saturated alcohols (e.g., citronellol). For the same leaving alcohol, 2‐[(ethylamino)carbonyl]benzoates cyclized faster than the corresponding 2‐(hydroxymethyl)benzoates, and much faster than their 2‐formyl and 2‐acetyl analogues (see, e.g., Fig. 4). Within the carbamoyl ester series, 2‐[(ethylamino)carbonyl]benzoates were found to have the highest rate constants for the alkaline ester hydrolysis, followed by unsubstituted 2‐(aminocarbonyl)benzoates, or the corresponding isopropyl derivatives. To rationalize the influence of the different structural changes on the hydrolysis kinetics, the experimental data obtained for the 2‐[(alkylamino)carbonyl]benzoates were compared with the results of density‐functional computer simulations (Table 2 and Scheme 4). Based on a preliminary semi‐empirical conformation analysis, density‐functional calculations at the B3LYP/6‐31G** level were carried out for the starting precursor molecules, several reaction intermediates, and the cyclized phthalimides. For the same precursor skeleton, these simple calculations were found to model the experimental data correctly. With an understanding of the influence of structural parameters on the rate constants obtained in this work, it is now possible to influence the rates of hydrolysis over several orders of magnitude, to design tailor‐made precursors for a large variety of fragrance alcohols, and to predict their efficiency as controlled‐release systems in practical applications.     

Polymer Structure‐Guided Self‐Assisted Preparation of Poly(ester‐thioether)‐Based Hollow Porous Microspheres and Hierarchically Interconnected Microcages for Drug Release

Porous polymer microspheres (PPMs) have been widely applied in various biomedical fields. Herein, the self‐assisted preparation of poly(ester‐thioether)‐based porous microspheres and hierarchical microcages, whose pore sizes can be controlled by varying the polymer structures, is reported. Poly(ester‐thioether)s with alkyl side chains (carbon atom numbers were 2, 4, and 8) can generate hollow porous microspheres; the longer alkyl chain length, the larger pore size of microspheres. The allyl‐modified poly(ester‐thioether) (PHBDT‐g‐C₃) can form highly open, hierarchically interconnected microcages. A formation mechanism of these PPMs is proposed; the hydrophobic side chains‐mediated stabilization of oil droplets dictate the droplet aggregation and following solvent evaporation, which is the key to the formation of PPMs. The hierarchically interconnected microcages of PHBDT‐g‐C₃ are due to the partially crosslinking of polymers. Pore sizes of PPMs can be further tuned by a simple mixing strategy of poly(ester‐thioether)s with different pore‐forming abilities. The potential application of these PPMs as H₂O₂‐responsive vehicles for delivery of hydrophobic (Nile Red) and hydrophilic (doxorubicin hydrochloride) cargos is also investigated. The microspheres with larger pore sizes show faster in vitro drug release. The poly(ester‐thioether)‐based polymer microspheres can open a new avenue for the design of PPMs and provide a H₂O₂‐responsive drug delivery platform.     

Bifunctional Aryloxylate Esters as potential oxidatively cleavable linkers

Selectively cleavable linkers are essential parts in environmentally responsive materials. Here, we introduce aryl oxalate esters (AOE) as one of the first examples for oxidatively cleavable linkers. To this end a series of novel AOEs was synthesized and explored regarding the H₂O₂-dependent degradation. All AOEs were cleaved selectively at the oxalate group. The degradation rate was clearly dependent on the substituents. Further, it was found that the H₂O₂ based degradation undergoes an autocatalysis mechanism.     

Role of hydrogen bonds in acid-catalyzed hydrolyses of esters

Acid-catalyzed ester hydrolyses were studied by means of DFT calculations. A model composed of ester and H₃O⁺(H₂O)₁₅ was adopted, and substrates esters are ethyl acetate, ethyl para-X-substituted benzoates (X?=?O₂N, Cl, H, iso-Bu, MeO, and Me₂N), and isobutyl benzoate. For the ethyl acetate, a stepwise path, precursor????TS1????Int1????Int2????TS2????product, was obtained. Here, TS is the transition state, and Int is the tetrahedral intermediate. The path is somewhat different from the established A_AC2 mechanism; the carbocation intermediate was calculated to be absent in the present model. The absence holds even for benzoates that may stabilize the cation except the X?=?Me₂N substituted one. At each local energy minimum, the cation character is retained in H₃O⁺. Proton relays along hydrogen bonds were found to prompt interchanges of covalent bonds. The rate-determining step is either TS1 for the electron-withdrawing X or TS2 for the electron-donating one.     

Darstellung und eigenschaften von diorganogermaniumdisulfinsäureestern

Diorganogermaniumdisulfinic esters of the type R₂Ge(O₂SR′)₂ (R = CH₃, R′ = CH₃, C₆H₅, p-CH₃C₆H₄; R = C₆H₅, R′ = CH₃, p-CH₃C₆H₄) which are sensitive to hydrolysis are obtained by reaction of the corresponding diorganogermanium dichlorides with anhydrous silver sulfinates. The newly prepared compounds are thoroughly investigated on the basis of their ¹H NMR, mass, IR and Raman spectra. The methyl ester (CH₃)₂Ge(O₂SCH₃)₂ is compared with the already known sulfinato complex of tin with the same formal composition.     

Reaction‐Based and Single Fluorescent Emitter Decorated Ratiometric Nanoprobe to Detect Hydrogen Peroxide

A novel reaction‐based cross‐linked polymeric nanoprobe with a self‐calibrating ratiometric fluorescence readout to selectively detect H₂O₂ is reported. The polymeric nanoprobe is fabricated by using hydrophobic H₂O₂‐reactive boronic ester groups, crosslinker units, and environmentally sensitive 3‐hydroxyflavone fluorophores through a miniemulsion polymerization. On treatment with H₂O₂, the boronic esters in the polymer are cleaved to form hydrophilic alcohols and subsequently lead to a hydrophobic–hydrophilic transition. Covalently linked 3‐hydroxyflavones manifest the change in polarity as a ratiometric transition from green to blue, accompanied by a 500‐fold increase in volume. Furthermore, this nanoprobe has been used for ratiometric sensing of glucose by monitoring the H₂O₂ generated during the oxidation of glucose by glucose oxidase, and thus successfully distinguished between normal and pathological levels of glucose.     

Über organogermaniumtrisulfinsäureester und versuche zur darstellung von tetrasulfinsäureestern des germaniums

The trisulfinic esters of germanium RGe(O₂SR′)₃ (R = R′ = CH₃; R = C₆H₅, R′ = CH₃, C₂H₅), which are sensitive to hydrolysis and temperature, are obtained by reaction of the corresponding trichlorides RGeCl₃ with anhydrous silver sulfinates. Aromatic trisulfinic esters as well as tetrasulfinic esters of germanium could not be obtained because of steric reasons. The esters, in which the RSO₂^?-residues are linked to germanium via oxygen, are investigated on the basis of their ¹H NMR, mass, IR and Raman spectra.     

Kinetics of base hydrolysis of α-amino acid esters catalyzed by palladium(II) piperazine complex

The kinetics of base hydrolysis of glycine, histidine, and methionine methyl esters in the presence of [Pd(pip)(H₂O)₂]²⁺ complex, where pip is piperazine, is studied in aqueous solutions, at T = 25°C, and I = 0.1 mol dm⁻³. The rate of ester hydrolysis for glycine methyl ester is studied at different temperature and dioxane/water solutions of different compositions. The kinetic data are fit under the assumption that the hydrolysis proceeds in one step. The activation parameters for the base hydrolysis of the complexes are evaluated      

Structure of the antibiotic Roridin E

Structure 1 has been established for roridin E (C₂₉H₃₈O₈), an antibiotic isolated from cultures of Myrothecium species. Base catalysed hydrolysis of 1 gave the known sesquiterpene alcohol verrucarol ( 4 ; C₁₅H₂₂O₄) and 2′-anhydrororidinic acid ( 6 ; C₁₄H₂₀O₆), a new dicarboxylic acid. The structure of 6 was determined by spectral analysis of its dimethyl ester 7 , dimethyl hexahydro-2′-anhydrororidinate ( 9 ), the acetyl derivative 10 , and the oxidation product 11 .     

2-Naphthol Moiety of Neocarzinostatin Chromophore as a Novel Protein-Photodegrading Agent and Its Application as a H2O2-Activatable Photosensitizer

A 2-naphthol derivative 2 corresponding to the aromatic ring moiety of neocarzinostatin chromophore was found to degrade proteins under photo-irradiation with long-wavelength UV light without any additives under neutral conditions. Structure–activity relationship studies of the derivative revealed that methylation of the hydroxyl group at the C2 position of 2 significantly suppressed its photodegradation ability. Furthermore, a purpose-designed synthetic tumor-related biomarker, a H₂O₂-activatable photosensitizer 8 possessing a H₂O₂-responsive arylboronic ester moiety conjugated to the hydroxyl group at the C2 position of 2 , showed significantly lower photodegradation ability compared to 2 . However, release of the 2 from 8 by reaction with H₂O₂ regenerated the photodegradation ability. Compound 8 exhibited selective photo-cytotoxicity against high H₂O₂-expressing cancer cells upon irradiation with long-wavelength UV light.     

Four oxoindole‐linked α‐alkoxy‐β‐amino acid derivatives

Four structures of oxoindolyl α‐hydroxy‐β‐amino acid derivatives, namely, methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐methoxy‐2‐phenylacetate, C₂₄H₂₈N₂O₆, (I), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐ethoxy‐2‐phenylacetate, C₂₅H₃₀N₂O₆, (II), methyl 2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐[(4‐methoxybenzyl)oxy]‐2‐phenylacetate, C₃₁H₃₄N₂O₇, (III), and methyl 2‐[(anthracen‐9‐yl)methoxy]‐2‐{3‐[(tert‐butoxycarbonyl)amino]‐1‐methyl‐2‐oxoindolin‐3‐yl}‐2‐phenylacetate, C₃₈H₃₆N₂O₆, (IV), have been determined. The diastereoselectivity of the chemical reaction involving α‐diazoesters and isatin imines in the presence of benzyl alcohol is confirmed through the relative configuration of the two stereogenic centres. In esters (I) and (III), the amide group adopts an anti conformation, whereas the conformation is syn in esters (II) and (IV). Nevertheless, the amide group forms intramolecular N—H...O hydrogen bonds with the ester and ether O atoms in all four structures. The ether‐linked substituents are in the extended conformation in all four structures. Ester (II) is dominated by intermolecular N—H...O hydrogen‐bond interactions. In contrast, the remaining three structures are sustained by C—H...O hydrogen‐bond interactions.