EMPIRICAL RULES FOR ^(31)p-NMR OF ORGANOPHOSPHORUS COMPOUNDS

The substituent effects on ^(31)P-NMR chemical shifts, are determined by five empirical rules. The proposed rules are based on that the shielding (upfield shift) of resonance nucleus is governed by the spherical symmetry of the electron cloud.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS 69.A NOVEL SYNTHESIS OF 5-SUBSTITUTED 3-(1'-DIETHOXYPHOSPHORYLALKYL)-2-ISOXAZOLINES

Additions of diethyl phosphite to α-nitroalkenes followed by the introduction of trimethylchlorosilane and an activated alkene, gave the corresponding title compounds via regioselective 1,3-dipolar cycloaddition in moderate yield.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS 86 SOME NEW ASPECTS ON THE SYNTHESIS OF DIALKYL 1-ISOCYANO-BENZYL-AND/OR ALKYL-PHOSPHONATES

1-Isocyano substituted benzylphosphonates were prepared by dehydration of 1-N-formylamino substituted benzylphosphonates,which were obtained by a tricomponental condensation described by us.Mean- while addition of diethyl phosphite to N-trityl aldimine followed by deprotection,formylation and dehydration gave corresponding 1-isocyano alkylphosphonates in one-pot procedure.

STUDIES ON ORGANOPHOSPHORUS COMPOUNDS XXXV——SUBSTITUENT EFFECT OF ORGANOPHOSPHORUS COMPOUNDS ON ^(31)P NMR SPECTROSCOPY

The linear relationship between the chemical shift of the resenant nucleus and the localvan der Waals steric energy calculated by molecular mechanics with MM2 force field wasextended to various organophosphorus compounds including alkyl-phosphates, -phosphonates,-phosphinates as well as -phosphine oxides. The conformational equilibria of a series of alkylO,O-1,3--propylene-and O, O-1,4-butylenephosphonates were studied by the molecular mechanicscalculations and the dynamic ^(31)P NMR spectroscopic method. As shown by these experimentaldata, the former existed in a chair form, and the latter in a twist boat form with an equatorialalkyl group in both configurations, either in gaseous state or in non-polar solvent.

Studies on organophosphorus compounds 52.Structure-reactivity studies of organophosphorus compounds by MNDO calculations

MNDO and MM2(85)methods were used to study the conformation and the structure- reactivity relationship of neutral and acidic phosphorus esters.The calculation results indicate that for the most stable conformation,the charge density of phosphoryl oxygen(q_O)is determined not only by the electronegativity of the substituents,but also by the conformation of the alkoxyl groups on the phosphorus atom.Meanwhile,the conformation of the alkoxyl group provides,as a rule, more important influence on the charge density of the phosphoryl oxygen.However,the energy of the highest occupied molecular orbital(EHOMO)is basically dependent on the eletronegativity of the substituents,while the donating ability or the withdrawing ability of the neutral phosphorus com- pounds is mainly governed by the EHOMO but not the q_O.This is also true for other kinds of the neutral oxygen-containing compounds.

Improving Sensitivity of Enzyme to Organophosphorous Compounds by Combining Experiment and Theory Methods

In this paper,we compared the sensitivities of AFEST（a thermophilic esterase from the archaea Archaeoglobus fulgidus） and acetylcholinesterase（AChE） towards five organophosphorus compounds（OPs） by means of molecular docking,and found that only the docking energy between AFEST and dichlorvos is lower than that between AChE and dichlorvos.Via the docking model of AFEST and dichlorvos,Arg43 was found to play an important role in the interaction between AFEST and dichlorvos by means of stabilizing the complex.Then mutant R43S was constructed,the IC 50（the concentration required to reduce virus-induced cytopathicity by 50% is estimated as 50% inhibitory concentration） of which to dichlorvos was lower than that of the wild type AFEST by a factor of 1.56,indicating the enhanced sensitivity of mutant R43S to dichlorvos.Combining of theory with experiment,we have obtained important structure-function information of AFEST,which will be helpful to the further studies of esterase.

Acute kidney injury from different poisonous substances

AIM To report our experience of acute kidney injury(AKI) developed after exposure to poisonous substance.METHODS Retrospective study where data was collected from case records of patients coming to this institute during January 1990 to May 2016.This institution is a tertiary care center for renal care in the metropolitan city of Karachi,Pakistan.History of ingested substance,symptoms on presentation,basic laboratory tests on arrival,mode of treatment and outcome were recorded from all patients and are presented here.Patients developing AKI after snake envenomation or scorpion stings are not included in this study.RESULTS During studied period 184 cases of AKI developing after poisoning were seen at our institution.The largest group was from paraphenyline diamine poisoning comprising 135 patients,followed by methanol in 8,organophosphorus compounds in 5,paraquat in 5,copper sulphate in 5,tartaric acid in 4,phenobarbitone in 3 and benzodiazipines,datura,rat killer,fish gall bladder,arsenic,boiler water,ammonium dichromate,acetic acid and herbs with lesser frequency.In 8 patients multiple substances were ingested in combination.Renal replacement therapy was required in 96% of patients.Complete recovery was seen in 72.28% patients,20% died during acute phase of illness.CONCLUSION It is important to report poisonous substances causing vital organ failure to increase awareness among general population as well as health care providers.

Brain injury due to acute organophosphate poisoning Magnetic resonance imaging manifestation and pathological characteristics

BACKGROUND： Acute organophosphate poisoning can cause injuries of multiple visceras; especially,central nervous system injury can increase risk factors of patients with severe acute organophosphate poisoning. An application of modem image may increase diagnostic rate of brain injury in an earlier period and provide evidences for clinical treatment.OBJECTIVE： To reveal imaging manifestations, pathological characteristics and multi-ways injured mechanism of brain injury due to acute organophosphate poisoning.DESIGN： Contrast observational study.SETTING： Department of Medical Image, the Second Hospital of Hebei Medical University.MATERIALS： The experiment was carried out in the Department of Nerve Molecule Imaging Medicine and Laboratory of Neurology, the Second Hospital of Hebei Medical University from August 2003 to February 2004. A total of 30 healthy cats weighing 2.8 - 3.5 g and of both genders were selected from Animal Experimental Center of Hebei Medical University.METHODS： Thirty healthy cats were randomly divided into control group （n =5） and intoxication group （n=25）. Cats in the control group were subcutaneously injected with 0.3 mL/kg saline at four points; while, cats in the intoxication group were subcutaneously injected with 400 g/L 0.3 mL/kg O,O-dimethyl-S-（methoxycarbonylmethyl） thiophosphate at four points. Two minutes after intoxication, cats received muscular injection with 0.5 mg/kg atropine sulfate, and then, brain tissues were collected from parietal lobe, basal ganglia, hippocampus, cerebellum and brain stem were observed at 3, 6, 24 hours, 3 and 7 days after intoxication respectively under optic microscope and electron microscope and expressions of acetylcholinesterase （AChE）, choline acetyltransferase （ChAT）, glial fibrillary acidic protein （GFAP）,glutamic acid （Glu） and γ-amino butyric acid after immunohistochemical staining.MAIN OUTCOME MEASURES： Results of MRI examinations; histological changes under optic microscope and electron microscope; expressions of AChE, ChAT, GFAP, Glu and γ -amino butyric acid after immunohistochemical staining.MAIN OUTCOME MEASURES： Results of MRI examinations; histological changes under optic microscope and electron microscope; expressions of AChE, ChAT, GFAP, Glu and γ -amino butyric acid after immunohistochemical staining.RESULTS： All 30 healthy cats were involved in the final analysis. ① Imaging and pathological observation： Image manifestations of brain injury induced by acute organophosphate poisoning showed as cerebral edema and symmetry signal abnormality of bilateral basal ganglia; while, pathological manifestations also showed as cerebral edema. ② Observation of immunohistochemical staining： As compared with the control group, after organophosphate poisoning, area of AChE immune-positive cells was decreased obviously （P〈0.01）, but area of ChAT immune-positive cells was not changed （P〉0.05）; in addition, positive cells of GFAP were increased remarkably （P〈0.01）, positive cells of γ -amino butyric acid in cerebral cortex were increased obviously （P〈0.05）, but numbers of positive cells of Glu were not changed （P〈0.05）.CONCLUSION： Multi-ways injured mechanism invovled in acute organophosphate poisoning. An application of modern image can increase diagnostic rate of brain injury in an earlier period and provide evidences for clinical treatment.

An efficient synthesis of substituted alkyl acrylates using α-keto amides

The addition of α-keto amides as a NH-acid to alkyl propiolates and dialkyl acetylenedicarboxylates in the presence of a catalytic amount of triphenylphosphine gives the corresponding substituted alkyl acrylates.

A review of sources,fate,levels,toxicity,exposure and transformations of organophosphorus flame-retardants and plasticizers in the environment

Organophosphate esters(OPEs)are esters of phosphoric acid that are increasingly used as plasticizers and by the flame-retardants industries as replacement for the regulated polybrominated diphenyl ethers.The most commonly classes of these pollutants are the chlorinated-and non-chlorinated-OPEs.The extent and magnitude of OPEs occurrence in the environment,combined with striking structural similarities to toxic organophosphorus pesticides has led to public concern over risk posed by these compounds.Using peer-reviewed literature published from the last decade(2010e2019),concentrations and distributions of commonly studied OPEs based on their occurrence in different matrices around the globe were evaluated and reported.These pollutants have a wide range of physicochemical properties such as their water solubility’s,logKow value,vapour pressure and bioconcentration factors(BCFs)which are very important factors in assessing their behaviour in different environmental matrices.Despite progress in research on OPEs over the years,full understanding of the environmental behaviour and fate of these pollutants are still elusive.Sources by which these pollutants enter the environment in conjunction with their concentrations together with their toxicities,estimated daily intakes,transformation products and fates are reviewed.It is envisaged that this review will heighten the importance of identifying emerging issues,data gaps and provide a future research agenda for OPEs.

Organophosphate pesticides an emerging environmental contaminant: Pollution, toxicity, bioremediation progress, and remaining challenges

Organophosphates(OPs)are an integral part of modern agriculture;however,due to overexploitation,OPs pesticides residues are leaching and accumulating in the soil,and groundwater contaminated terrestrial and aquatic food webs.Acute exposure to OPs could produce toxicity in insects,plants,animals,and humans.OPs are known for covalent inhibition of acetylcholinesterase enzyme in pests and terrestrial/aquatic organisms,leading to nervous,respiratory,reproductive,and hepatic abnormalities.OPs pesticides also disrupt the growth-promoting machinery in plants by inhibiting key enzymes,permeability,and trans-cuticular diffusion,which is crucial for plant growth.Excessive use of OPs,directly/indirectly affecting human/environmental health,raise a thoughtful global concern.Developing a safe,reliable,economical,and eco-friendly methods for removing OPs pesticides from the environment is thus necessary.Bioremediation techniques coupled with microbes or microbial-biocatalysts are emerging as promising antidotes for OPs pesticides.Here,we comprehensively review the current scenario of OPs pollution,their toxicity(at a molecular level),and the recent advancements in biotechnology(modified biocatalytic systems)for detection,decontamination,and bioremediation of OP-pesticides in polluted environments.Furthermore,the review focuses on onsite applications of OPs degrading enzymes(immobilizations/biosensors/others),and it also highlights remaining challenges with future approaches.

Samarium-153-EDTMP bone uptake rate and its relation to therapeutic effect

OBJECTIVE: To evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect. METHODS: Sixty-six patients with painful bony metastases from prostate (n = 15), lung (n = 20), breast (n= 18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of (153)Sm-EDTMP. Bone uptake rate was then calculated. (1 ) Complete response (CR): disappearance of > 2 metastases, Karnofsky Performance Score (KPS) increase > 20, moderate or complete remission of bone pain 7 d post injection of (153)Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase

Comparative analysis of patients not responding to a single dose of ^(153)Sm-EDTMP palliative treatment for painful skeletal metastases

Objective A certain fraction of patients failed palliative treatment of 153Sm-ethylenediaminetetramethy lenephosphate ( 153Sm-EDTMP) for painful skeletal metastases were reviewd. A comparative analysis was designed to identify the factors related to therapeutic response. Methods From a 3-year multi-center clinical trial, 51 cases were collected who did not respond to an intravenous injection of 153Sm-EDTMP at a dosage of 0.5-1.5 mCi/kg. The therapeutic efficacy was evaluated via changes of symptoms, general condition, consumption of analgesics, sum of effect product, and Karnofsky scores. The age, sex, history of treatment, tumor type, location of bony involvement, uptake ratio and number of metastases, and doses used by the patients were compared to those of the responders. Results In 51 non-responders, 43 were male, 34 suffered from lung cancer, 41 had bone lesions in the vertebrae, 39 in the pelvis, and 24 had metastases in the lower extremities. Sex distribution, tumor type and location of the lesion differed significantly between responders and non-responders. No other factor showed differences between the two groups. Though patients of younger age, and lesions with lower uptake of radiopharmaceutical seemed to fail the treatment more easily as observed clinically, this was not confirmed by statistical analysis. Conclusion The sex of the patients, certain types of primary tumors and metastases to lower parts of the body were found to influence the patients’ response to a single dose of 153Sm-EDTMP palliation. Further exploration of a better way to determine dosage and predict response for each individual case is needed.

Phosphafluorenyl lithiums:direct synthesis from white phosphorus,structure and diversified synthons

While rich chemistry of phospholyl anions is discovered,phosphafluorenyl anions are only proposed as the critical intermediates for the synthesis of phosphafluorenes.In this article,we reported the direct synthesis of phosphafluorenyl lithiums from white phosphorus(P_(4))through direct P-C bond formation.The reaction between P4 and biphenyl dilithio reagents efficiently afforded phosphafluorenyl lithiums,which were further used to synthesize different kinds of organophosphorus compounds.The aggregation states of phosphafluorenyl lithiums were investigated for the first time.Mechanistic studies by DFT calculations revealed a cooperative nucleophilic attack of two C−Li bonds on P_(4)molecule.

Black Phosphorus: An Effective Feedstock for the Synthesis of Phosphorus-Based Chemicals

We propose and demonstrate the novel concept of synthesizing organophosphorus compounds directly from black phosphorus(BP)nanoparticles as the feedstock.Compounds such as alkyl phosphines,alkyl phosphine oxides,phosphine sulfide,and hexafluorophosphate anion are prepared with good isolation yields under mild conditions.Selective synthesis of primary,secondary,and tertiary organophosphorus compounds is also demonstrated utilizing this one-pot approach.Reaction mechanisms are proposed and discussed.Compared with traditional white phosphorus(P 4)-based methods,the new synthetic concept and process utilizing elemental phosphorus are more efficient and environmentally friendly.

Cloud point extraction coupled with back extraction: a green methodology in analytical chemistry

Recently, cloud point extraction (CPE) coupled with back extraction (BE) has been suggestedas a promising alternative to liquid-liquid extraction. In CPE, non-ionic surfactants in aqueoussolutions form micelles and the solution becomes turbid when heated to the cloud pointtemperature. Microwave- or ultrasonic-assisted BE can be performed after CPE and beforeinjection of the sample for instrumental analysis by ultraviolet-visible spectroscopy, high-performance liquid chromatography, gas chromatography, gas chromatography-mass spectrometry, or liquid chromatography-mass spectrometry. This article reviews selected publishedscientific research on the application of CPE-BE to the determination of alkaloids, drugs andorganophosphorus compounds from several complex matrices. This method could bescaled-up for use in forensic science.