First-principles studies on two-dimensional B3O3 adsorbent as a potential drug delivery platform for TEPA anticancer drug.

The remarkable properties of pristine B3O3 nanosheet as a nanocarrier for adsorption and desorption of TEPA anticancer drug for designing potential drug delivery platform were investigated using periodic DFT calculations. We studied the adsorption energy of all stable complexes formed between the drug molecule and B3O3 in gas and aqueous phases along with electronic structure analysis of complexes. Different adsorption configurations were studied for drug/B3O3 complexes, including the interaction of the C atom of the triangular ring, O atom in the TEPA drug with the B atom in B3O3, and indirect drug interaction the middle of the R1 ring cavity of the B3O3 nanosheet. The take-up of TEPA prompts a substantial change of 68.13% in the band gap (Eg) of the B3O3 nanosheet in the most stable complex. The present study results affirmed the application of B3O3 nanosheet as a potential vehicle for TEPA drugs in the treatment of cancerous tissues.

A novel sandwich aptasensor for detecting T-2 toxin based on rGO-TEPA-Au@Pt nanorods with a dual signal amplification strategy.

T-2 toxin is a mycotoxin that can cause chronic illnesses, and the detection of T-2 toxin in food is critical for human health. Herein, a novel sandwich aptasensor with a dual signal amplification strategy was developed for the detection of T-2 toxin. Molybdenum disulfide-polyaniline-chitosan-gold nanoparticles (MoS2-PANI-Chi-Au) were processed to the modified glassy carbon electrode (GCE) and used as the aptasensor platform to expedite the electronics transport and immobilize the amino-terminated capture DNA probe by Au-N bonds. The reduced graphene oxide-tetraethylene pentamine-gold@platinum nanorods (rGO-TEPA-Au@Pt NRs) were first synthesized and immobilized with a signal DNA probe. Once T-2 toxin was added into the biosensing system, the aptamer would trap T-2 toxin to turn the signal off. Next, dissociative aptamer hybridized with the capture DNA probe in GCE and linked simultaneously to the signal DNA probe on rGO-TEPA-Au@Pt NRs with another end sequence of aptamer to turn the signal on. Owing to the efficient catalytic ability of bimetallic Au@Pt nanorods, the signal was perfectly amplified through the catalysis of hydrogen peroxide (H2O2) and recorded by chronoamperometry. With the outstanding augment response, the limit of detection reached 1.79 fg mL-1 (3SB/m) and a wide linear range from 10 fg mL-1 to 100 ng mL-1 was presented. The sensitivity of the aptasensor was 19.88 µA⋅µM-1⋅cm-2. Meanwhile, the DNA aptamer-bimetallic nanorod based sensing system presented excellent specificity. The developed aptasensor provides a new platform for T-2 toxin detection with low cost for real sample assays.

Mechanisms and kinetics of thiotepa and tepa hydrolysis: DFT study.

N,N',N″-triethylenethiophosphoramide (Thiotepa) and its oxo analogue (Tepa) as the major metabolite are trifunctional alkylating agents with a broad spectrum of antitumor activity. In vivo and vitro studies show alkylation of DNA by Thiotepa and Tepa can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. In pathway 1, these agents are capable of forming cross-links with DNA molecules via two different mechanisms. In the first mechanism, the ring opening reaction is initiated by protonating the aziridine, which then becomes the primary target of nucleophilic attack by the N7-Guanine. The second one is a direct nucleophilic ring opening of aziridyl group. Thiotepa and Tepa in pathway 2, act as a cell penetrating carrier for aziridine, which is released via hydrolysis. The released aziridine can form a cross-link with N7-Guanine. In this study, we calculated the activation free energy and kinetic rate constant for hydrolysis of these agents and explored interaction of aziridine with Guanine to predict the most probable mechanism by applying density functional theory (DFT) using B3LYP method. In addition, solvent effect was introduced using the conductor-like polarizable continuum model (CPCM) in water, THF and diethylether. Hyperconjugation stabilization factors that have an effect on stability of generated transition state were investigated by natural bond order (NBO) analysis. Furthermore, quantum theory of atoms in molecules (QTAIM) analysis was performed to extract the bond critical points (BCP) properties, because the electron densities can be considered as a good description of the strength of different types of interactions.

Stability of thioTEPA and its metabolites, TEPA, monochloroTEPA and thioTEPA-mercapturate, in plasma and urine.

The degradation of N,N',N"-triethylenethiophosphoramide (thioTEPA) and its metabolites N,N',N"-triethylenephosphoramide (TEPA), N, N'-diethylene,N"-2-chloroethylphosphoramide (monochloroTEPA) and thioTEPA-mercapturate in plasma and urine has been investigated. ThioTEPA, TEPA and monochloroTEPA were analyzed using a gas chromatographic (GC) system with selective nitrogen/phosphorous detection; thioTEPA-mercapturate was analyzed on a liquid chromatography-mass spectrometric (LC-MS) system. The influences of pH and temperature on the stability of thioTEPA and its metabolites were studied. An increase in degradation rate was observed with decreasing pH as measured for all studied metabolites. In urine the rate of degradation at 37 degrees C was approximately 2.5+/-1 times higher than at 22 degrees C. At 37 degrees C thioTEPA and TEPA were more stable in plasma than in urine, with half lives ranging from 9-20 h for urine and 13-34 h for plasma at pH 6. Mono- and dichloro derivatives of thioTEPA were formed in urine and the monochloro derivative was found in plasma. Degradation of TEPA in plasma and urine resulted in the formation of monochloroTEPA. During the degradation of TEPA in plasma also the methoxy derivative of TEPA was formed as a consequence of the applied procedure. The monochloro derivative of thioTEPA-mercapturate was formed in urine, whereas for monochloroTEPA no degradation products could be detected.

The degradation of N,N',N"-triethylenephosphoramide in aqueous solutions: a qualitative and kinetic study.

The degradation of N,N',N"-triethylenephosphoramide (TEPA) in aqueous solutions has been investigated over a pH range of 3-14. Samples were analyzed using a gas chromatographic system with nitrogen/phosphorus selective detection. The degradation kinetics were studied as function of pH, sodium chloride concentration and temperature. The degradation of TEPA in buffers follows pseudo first order kinetics. The logk(obs)8 the methoxy derivative of TEPA was formed, as a consequence of the applied procedure.

Alkylation of DNA with aziridine produced during the hydrolysis of N,N',N''-triethylenethiophosphoramide.

A reaction pathway by which thiotepa (N,N',N''-triethylenethiophosphoramide) and tepa (N,N',N''-triethylenethiophosphoramide), its major metabolite in humans, alkylate and depurinate DNA involves hydrolysis to aziridine (ethylene imine), a highly reactive monofunctional alkylating agent. Hydrolytic cleavage of an N-P bond of thiotepa releases aziridine which reacts with DNA, resulting in depurination and formation of the stable N-7 adduct 7-(2-aminoethyl)guanine and an aminoethyl adduct of adenine. Chromatographically identical alkylated products were observed in the reaction of thiotepa and tepa with individual nucleosides. Adducts with deoxycytidine or thymidine were not detected. Aziridine was measured by HPLC after derivatization with 1,2-naphthoquinone 4-sulfate. On the basis of the identity of the DNA adducts and the rate of formation of aziridine by hydrolysis in vitro, thiotepa is concluded to be a lipophilic, stabilized form of aziridine which serves as a cell-penetrating carrier of aziridine.