Optimized calculations of 75 PCDDs and their parent DD were carded out at the B3LYP/6-31G＊ level by density functional theory （DFT） method. The structural parameters were obtained and significant correlation betwee...Optimized calculations of 75 PCDDs and their parent DD were carded out at the B3LYP/6-31G＊ level by density functional theory （DFT） method. The structural parameters were obtained and significant correlation between the C1 substitution position and some structural parameters was found. Consequently, the number of C1 substitution positions was taken as theoretical descriptors to establish two novel QSPR models for predicting lgKow and -lgSw of all PCDD congeners. The two models achieved in this work contain two variables （Na and Nβ）, of which r = 0.9312, 0.9965 and SD = 0.27, 0.12 respectively, and t values are all large. The variation inflation factors （VIF） of variables in the two models herein are both less than 5.0, suggesting high accuracy of the lgKow and -lgSw predicting models, and the results of cross-validation test also show that the two models exhibit optimum stability and good predictive power. By comparison, the correlation and predictive ability of the present work are more advantageous than those obtained using semi-empirical AM1 and GC-RI methods.展开更多
Optimized calculations of 209 polychlorinated diphenyl ethers （PCDEs） and diphenyl ethers were carried out at the B3LYP/6-31G^＊ level with the Gaussian 98 program. Based on the theoretical linear solvation energy r...Optimized calculations of 209 polychlorinated diphenyl ethers （PCDEs） and diphenyl ethers were carried out at the B3LYP/6-31G^＊ level with the Gaussian 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting aqueous solubility （-lgSw） of PCDEs. The model obtained in this work contains two variables： mean molecular polarizability （a） and the most positive partial charge on a hydrogen atom （qH^＋）, of which RE = 0.9606 and SD = 0.32. And the results of cross-validation test also show that the model exhibits optimum stability and better predictive power. Moreover, the predictive power of the new model is better than that of MCIs method.展开更多
Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some struct...Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some structural parameters. Consequently, Cl substitution positions were taken as theoretical descriptors to establish a novel QSPR model for predicting –lgSw of all PCB congeners. The model achieved in this work contains four variables, of which r^2 = 0.9527, q^2 = 0.9490 and SD = 0.25 with large t values. In addition, the variation inflation factors （VIFs） of variables in this model are all less than 5.0, suggesting high accuracy of the –lgSw predicting model. And the results of cross-validation test and method validation also show that the model exhibits optimum stability and better predictive capability than that from the AM1 method.展开更多
The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents(DESs) on the aqueous solubility of curcumin(C...The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents(DESs) on the aqueous solubility of curcumin(CUR) via experiment and theoretical calculation. Choline chloride-based DESs with polyols 1,2-propanediol(1,2-PDO), 1,3-propanediol, ethylene glycol, and glycerol as hydrogen bond donors were prepared and used as co-solvents. The CUR aqueous solubility increased with increasing the DESs content at temperature of 303.15-318.15 K, especially in aqueous ChCl/1,2-PDO(mole ratio 1:4) solutions. The positive apparent molar volume values and reduced density gradient analysis confirmed the existence of strong interactions between CUR and solvent. The van der Waals interactions and hydrogen bonding coexisted in DESs monomer retained the stability of DESs structure after introducing CUR. Moreover,the lower interaction energy of DESs…CUR system than that of the counterpart DESs further proved the strong interaction between CUR and DESs. The lowest interaction energy of ChCl/1,2-PDO…CUR system indicated that this system was the most stable and ChCl/1,2-PDO was promising for CUR dissolution.This work provides efficient solvents for utilizing curcumin, contributing to a deep insight into the interactions between DES and CUR at the molecular level, and the role of DESs on enhancing drugs solubility.展开更多
The thermodynamic relationships among aqueous solubility and molar volume (MV) , total molecular surface area (TSA) and molecular connectivity index (MCI) for highly hydrophobic chemicals. PCBs are established and dis...The thermodynamic relationships among aqueous solubility and molar volume (MV) , total molecular surface area (TSA) and molecular connectivity index (MCI) for highly hydrophobic chemicals. PCBs are established and discussed, respectively. Good linear relationships exist among In Cs and MV, TSA or MCI.展开更多
Optimized calculation of dibenzofuran （DF） and 135 polychlorinated dibenzofurans （PCDFs） was carried out at the B3LYP/6-31G＊ level in GAUSSIAN 98 program. Based on the theoretical linear solvation energy relation...Optimized calculation of dibenzofuran （DF） and 135 polychlorinated dibenzofurans （PCDFs） was carried out at the B3LYP/6-31G＊ level in GAUSSIAN 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel quantitative structureproperty relationship （QSPR） model for predicting n-octanol/water partition coefficients （lgKow） of PCDFs. The new model of lgKow achieved in this work contains three variables： energy of the highest occupied molecular orbital （EHOMO）, the most negative atomic partial charge （q^-） and average molecular polarizability （a）, of which R^2= 0.9011 and SD = 0,17 with larger t values. In addition, the variation inflation factors （VIF） of variables in the present model are all less than 5.5, suggesting high accuracy of the lgKow model. And the results of cross-validation test （q^2 = 0.8688） and method validation also show this model exhibits optimum stability and better predictive power than semi-empirical method. At the same time, it is found that the aqueous solubility （-lgSw） has high relative correlation with constant volume molar heat capacity （Cv^0）, of which R^2 = 0.9777 and SD = 0.22. Moreover, lgKow and -lgSw values of all PCDF congeners were predicted respectively.展开更多
Using the molecular electronegativity distance vector descriptors derived directly from the molecular topological structures, the aqueous solubilities of polychlorinated biphenyls (PCBs) were predicted. A three-variab...Using the molecular electronegativity distance vector descriptors derived directly from the molecular topological structures, the aqueous solubilities of polychlorinated biphenyls (PCBs) were predicted. A three-variable regression equation with correlation coefficient of 0.9739 and the root mean square errors of 0.26 was developed. The descriptors included in the equation represent three interactions between three pairs of atomic types, i.e., atom -C= and >C=, -C= and -Cl, and -Cl and -Cl. It has been proved that the aqueous solubilities of 137 PCB congeners can be accurately predicted as long as there are more than 65 calibration compounds.展开更多
Resveratrol has received widespread attention due to its health benefits,but its practical application is limited due to the poor stability and low bioavailability.In this study,we synthesized a series of complexes(CR...Resveratrol has received widespread attention due to its health benefits,but its practical application is limited due to the poor stability and low bioavailability.In this study,we synthesized a series of complexes(CR)by coupling resveratrol with crab shell-derived carbon dots(C-CDs),and the impacts of the interaction between C-CDs and resveratrol on the properties of CR were investigated systematically.Results revealed that resveratrol quenched C-CDs through the inner filter effect and static quenching mechanisms.The aqueous solubility and photostability of resveratrol were improved significantly by C-CDs(P<0.05).The aqueous solubility of CR with 40 mg resveratrol(CR4)was 9.03 times that of free resveratrol,and the ultraviolet light stability was 34.06%higher than that of free resveratrol.Moreover,antioxidant and antibacterial properties of resveratrol were improved by the quenching of C-CDs.The scavenging rate of ABTS^(+)free radicals by CR4 at 50μg/mL resveratrol-equivalent was improved largely due to the increment of aqueous solubility for resveratrol,reaching 97.87%.CR4 exhibited obvious antibacterial effects on combating spoilage bacteria such as Staphylococcus aureus.These results suggest that C-CDs can be an appropriate nanocarrier to enhance the aqueous solubility,photostability,antioxidant activity,and antibacterial capacity of hydrophobic bioactive ingredients.展开更多
A two-liquid-phase （TLP） soil slurry system was employed to quantify the efficiencies of autoclaving and mercuric chloride sterilization in the dissipation of polycyclic aromatic hydrocaxbons （PAHs）. The fates of ...A two-liquid-phase （TLP） soil slurry system was employed to quantify the efficiencies of autoclaving and mercuric chloride sterilization in the dissipation of polycyclic aromatic hydrocaxbons （PAHs）. The fates of 11 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo（a）anthracene, benzo（a）pyrene, benzo（b）fluoranthene, benzo（k）fluoranthene, dibenzo（a, h）anthracene） were recorded over 113 days of incubation. No microorganisms were detected in the HgC12-sterilized soil slurries during the whole incubation period, indicating very effective sterilization. However, about 2% 36% losses of PAHs were observed in the HgCl2- sterilized slurry. In contrast to the HgCl2-sterilized soil slurry, some microorganisms survived in the autoclaved soil slurries. Moreover, significant biodegradiation of 6 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene and pyrene） was observed in the autoclaved soil slurries. This indicated that biodegradation results of PAHs in the soil slurries, calculated on basis of the autoclaved control, would be underestimated. It could be concluded that the sterilization efficiency and effectiveness of HgCl2 on soil slurry was much higher than those of autoclaving at 121 ℃ for 45 rain.展开更多
Structural parameters of 36 fluorobenzene, chlorobenzene and bromobenzene compounds were computed at the B3LYP/6-31G^＊ level with DFT method. Based on the experimental data of aqueous solubility （–lgSw） and n-octa...Structural parameters of 36 fluorobenzene, chlorobenzene and bromobenzene compounds were computed at the B3LYP/6-31G^＊ level with DFT method. Based on the experimental data of aqueous solubility （–lgSw） and n-octanol/water partition coefficient （lgKow）, using the modified theoretical linear solvation energy relation （MTLSER） model, correlation equations that can predict –lgSw and lgKow were developed using structural parameters as theoretical descriptors. The correlation coefficients （r） of these equations are 0.9728 and 0.9967, respectively. These equations were further validated by variance inflation factors （VIF） and t-test methods and then used to predict –lgSw and lgKow values. By comparison, the correlation and predictive ability of our work are more advantageous than those calculated from valence molecular connectivity indices method and molecular topology index method.展开更多
The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certa...The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.展开更多
Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase...Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase(PDK)inhibitors 4-phenylbutyrate(PhB,2b)or dichloroacetate(DCA,2c)),and their di-axial functionalised analogues with OR_(1)=DCA and OR_(2)=cou(3a),PhB(3b),or DCA(3c)have been synthesised and characterised,including the X-ray crystal structures of complexes 2a,3a,3b and 3c.These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II)species and free radicals selectively in cancer cells when irradiated.Mono-functionalised complexes 2a-2c showed higher aqueous solubility and more negative reduction potentials.Mono-and di-functionalised complexes displayed higher photocytotoxicity with blue light(1 h,465 nm,4.8 mW cm^(-2))than the parent dihydroxido complex 1(OR_(1)=OR_(2)=OH)in A2780 human ovarian(IC_(50)0.9-2.9μM for 2a-2c;0.11-0.39μM for 3a-3c)and A549 human lung cancer cells(5.4-7.8μM for 2a-2c;1.2-2.6μM for 3a-3c)with satisfactory dark stability.Notably,no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes(IC_(50)>20μM).Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations.展开更多
Cyclometalated Ir(III)complexes hold great promise as an alternative to platinum metallodrugs for the therapy and diagnosis of cancer.However,their low aqueous solubility and poor cell membrane permeability are obstac...Cyclometalated Ir(III)complexes hold great promise as an alternative to platinum metallodrugs for the therapy and diagnosis of cancer.However,their low aqueous solubility and poor cell membrane permeability are obstacles for in vivo applications.Here we have encapsulated for the first time,using polyurethane–polyurea hybrid nanocapsules(NCs),two phosphorescent tris-cyclometalated Ir(III)complexes incorporating deprotonated 2-arylbenzimidazole ligands,Ir1 and Ir2.Ir(III)-Loaded nanocapsules(NC-Ir1 and NC-Ir2)showed a roughly round shape and controlled particle size distribution around 18 nm.The photophysical properties of aqueous solutions of NCs were similar to those of the free complexes in CH2Cl2,which accounts for the hydrophobic and protective environment generated by the nanoparticles around the cargo.Nanoencapsulation had also a positive effect on the cellular uptake of the metallodrugs and NCs were found to be highly cytotoxic towards several cancer cell lines,whereas Ir(III)complexes alone were found to be inactive.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 20737001)(2003CB415002)China Postdoctoral Science Foundation (No. 2003033486)
文摘Optimized calculations of 75 PCDDs and their parent DD were carded out at the B3LYP/6-31G＊ level by density functional theory （DFT） method. The structural parameters were obtained and significant correlation between the C1 substitution position and some structural parameters was found. Consequently, the number of C1 substitution positions was taken as theoretical descriptors to establish two novel QSPR models for predicting lgKow and -lgSw of all PCDD congeners. The two models achieved in this work contain two variables （Na and Nβ）, of which r = 0.9312, 0.9965 and SD = 0.27, 0.12 respectively, and t values are all large. The variation inflation factors （VIF） of variables in the two models herein are both less than 5.0, suggesting high accuracy of the lgKow and -lgSw predicting models, and the results of cross-validation test also show that the two models exhibit optimum stability and good predictive power. By comparison, the correlation and predictive ability of the present work are more advantageous than those obtained using semi-empirical AM1 and GC-RI methods.
基金funded by the 973 National Basic Research Program of China (2003CB415002)China Postdoctoral Science Foundation (No. 2003033486)
文摘Optimized calculations of 209 polychlorinated diphenyl ethers （PCDEs） and diphenyl ethers were carried out at the B3LYP/6-31G^＊ level with the Gaussian 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting aqueous solubility （-lgSw） of PCDEs. The model obtained in this work contains two variables： mean molecular polarizability （a） and the most positive partial charge on a hydrogen atom （qH^＋）, of which RE = 0.9606 and SD = 0.32. And the results of cross-validation test also show that the model exhibits optimum stability and better predictive power. Moreover, the predictive power of the new model is better than that of MCIs method.
基金This work was supported by the 973 National Basic Research Program of China (2003CB415002)the China Postdoctoral Science Foundation (No. 2003033486)
文摘Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some structural parameters. Consequently, Cl substitution positions were taken as theoretical descriptors to establish a novel QSPR model for predicting –lgSw of all PCB congeners. The model achieved in this work contains four variables, of which r^2 = 0.9527, q^2 = 0.9490 and SD = 0.25 with large t values. In addition, the variation inflation factors （VIFs） of variables in this model are all less than 5.0, suggesting high accuracy of the –lgSw predicting model. And the results of cross-validation test and method validation also show that the model exhibits optimum stability and better predictive capability than that from the AM1 method.
基金financially supported by the National Natural Science Foundation of China (21905069, U21A20307, 22208073)the Shenzhen Science and Technology Innovation Committee (ZDSYS20190902093220279, KQTD20170809110344233, GXWD20201230155427003-20200821181245001, GXWD20201230155427003-202008211 81809001, ZX20200151)the Department of Science and Technology of Guangdong Province (2020A1515110879)。
文摘The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents(DESs) on the aqueous solubility of curcumin(CUR) via experiment and theoretical calculation. Choline chloride-based DESs with polyols 1,2-propanediol(1,2-PDO), 1,3-propanediol, ethylene glycol, and glycerol as hydrogen bond donors were prepared and used as co-solvents. The CUR aqueous solubility increased with increasing the DESs content at temperature of 303.15-318.15 K, especially in aqueous ChCl/1,2-PDO(mole ratio 1:4) solutions. The positive apparent molar volume values and reduced density gradient analysis confirmed the existence of strong interactions between CUR and solvent. The van der Waals interactions and hydrogen bonding coexisted in DESs monomer retained the stability of DESs structure after introducing CUR. Moreover,the lower interaction energy of DESs…CUR system than that of the counterpart DESs further proved the strong interaction between CUR and DESs. The lowest interaction energy of ChCl/1,2-PDO…CUR system indicated that this system was the most stable and ChCl/1,2-PDO was promising for CUR dissolution.This work provides efficient solvents for utilizing curcumin, contributing to a deep insight into the interactions between DES and CUR at the molecular level, and the role of DESs on enhancing drugs solubility.
文摘The thermodynamic relationships among aqueous solubility and molar volume (MV) , total molecular surface area (TSA) and molecular connectivity index (MCI) for highly hydrophobic chemicals. PCBs are established and discussed, respectively. Good linear relationships exist among In Cs and MV, TSA or MCI.
基金This work was supported by the China Postdoctoral Science Foundation (No. 2003033486)
文摘Optimized calculation of dibenzofuran （DF） and 135 polychlorinated dibenzofurans （PCDFs） was carried out at the B3LYP/6-31G＊ level in GAUSSIAN 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel quantitative structureproperty relationship （QSPR） model for predicting n-octanol/water partition coefficients （lgKow） of PCDFs. The new model of lgKow achieved in this work contains three variables： energy of the highest occupied molecular orbital （EHOMO）, the most negative atomic partial charge （q^-） and average molecular polarizability （a）, of which R^2= 0.9011 and SD = 0,17 with larger t values. In addition, the variation inflation factors （VIF） of variables in the present model are all less than 5.5, suggesting high accuracy of the lgKow model. And the results of cross-validation test （q^2 = 0.8688） and method validation also show this model exhibits optimum stability and better predictive power than semi-empirical method. At the same time, it is found that the aqueous solubility （-lgSw） has high relative correlation with constant volume molar heat capacity （Cv^0）, of which R^2 = 0.9777 and SD = 0.22. Moreover, lgKow and -lgSw values of all PCDF congeners were predicted respectively.
文摘Using the molecular electronegativity distance vector descriptors derived directly from the molecular topological structures, the aqueous solubilities of polychlorinated biphenyls (PCBs) were predicted. A three-variable regression equation with correlation coefficient of 0.9739 and the root mean square errors of 0.26 was developed. The descriptors included in the equation represent three interactions between three pairs of atomic types, i.e., atom -C= and >C=, -C= and -Cl, and -Cl and -Cl. It has been proved that the aqueous solubilities of 137 PCB congeners can be accurately predicted as long as there are more than 65 calibration compounds.
基金supported by the National Natural Science Founda-tion of China(32302129).
文摘Resveratrol has received widespread attention due to its health benefits,but its practical application is limited due to the poor stability and low bioavailability.In this study,we synthesized a series of complexes(CR)by coupling resveratrol with crab shell-derived carbon dots(C-CDs),and the impacts of the interaction between C-CDs and resveratrol on the properties of CR were investigated systematically.Results revealed that resveratrol quenched C-CDs through the inner filter effect and static quenching mechanisms.The aqueous solubility and photostability of resveratrol were improved significantly by C-CDs(P<0.05).The aqueous solubility of CR with 40 mg resveratrol(CR4)was 9.03 times that of free resveratrol,and the ultraviolet light stability was 34.06%higher than that of free resveratrol.Moreover,antioxidant and antibacterial properties of resveratrol were improved by the quenching of C-CDs.The scavenging rate of ABTS^(+)free radicals by CR4 at 50μg/mL resveratrol-equivalent was improved largely due to the increment of aqueous solubility for resveratrol,reaching 97.87%.CR4 exhibited obvious antibacterial effects on combating spoilage bacteria such as Staphylococcus aureus.These results suggest that C-CDs can be an appropriate nanocarrier to enhance the aqueous solubility,photostability,antioxidant activity,and antibacterial capacity of hydrophobic bioactive ingredients.
基金Supported by the National High Technology Research and Development Program (863 Program) of China (No. 2007AA061101)the National Natural Science Foundation of China (Nos. 20707028,4092106,40771104 and 40701078)
文摘A two-liquid-phase （TLP） soil slurry system was employed to quantify the efficiencies of autoclaving and mercuric chloride sterilization in the dissipation of polycyclic aromatic hydrocaxbons （PAHs）. The fates of 11 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo（a）anthracene, benzo（a）pyrene, benzo（b）fluoranthene, benzo（k）fluoranthene, dibenzo（a, h）anthracene） were recorded over 113 days of incubation. No microorganisms were detected in the HgC12-sterilized soil slurries during the whole incubation period, indicating very effective sterilization. However, about 2% 36% losses of PAHs were observed in the HgCl2- sterilized slurry. In contrast to the HgCl2-sterilized soil slurry, some microorganisms survived in the autoclaved soil slurries. Moreover, significant biodegradiation of 6 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene and pyrene） was observed in the autoclaved soil slurries. This indicated that biodegradation results of PAHs in the soil slurries, calculated on basis of the autoclaved control, would be underestimated. It could be concluded that the sterilization efficiency and effectiveness of HgCl2 on soil slurry was much higher than those of autoclaving at 121 ℃ for 45 rain.
基金Project supported by the 973 National Basic Research Program of China (2003CB415002)the Chinese Postdoctoral Science Foundation (No. 2003033486)
文摘Structural parameters of 36 fluorobenzene, chlorobenzene and bromobenzene compounds were computed at the B3LYP/6-31G^＊ level with DFT method. Based on the experimental data of aqueous solubility （–lgSw） and n-octanol/water partition coefficient （lgKow）, using the modified theoretical linear solvation energy relation （MTLSER） model, correlation equations that can predict –lgSw and lgKow were developed using structural parameters as theoretical descriptors. The correlation coefficients （r） of these equations are 0.9728 and 0.9967, respectively. These equations were further validated by variance inflation factors （VIF） and t-test methods and then used to predict –lgSw and lgKow values. By comparison, the correlation and predictive ability of our work are more advantageous than those calculated from valence molecular connectivity indices method and molecular topology index method.
基金financially supported by the National Natural Science Foundation of China(Nos.21434008,21374054)National Basic Research Program of China(973 Program,No.2014CB932202)
文摘The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the vip of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the vip copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.
基金support from the EPSRC(EP/G006792,EP/F034210/1 for PJS)University of Warwick(Chancellor’s International PhD Scholarship for HS)Anglo-American Platinum(HS)and Wellcome Trust(grant no 209173/Z/17/Z,Sir Henry Wellcome Fellowship for CI).
文摘Mono-axial functionalised octahedral diazido Pt(IV)complexes trans,trans,trans-[Pt(py)_(2)(N_(3))_(2)(OR_(1))(OR_(2))](OR_(1)=OH and OR_(2)=anticancer agent coumarin-3 carboxylate(cou,2a),pyruvate dehydrogenase kinase(PDK)inhibitors 4-phenylbutyrate(PhB,2b)or dichloroacetate(DCA,2c)),and their di-axial functionalised analogues with OR_(1)=DCA and OR_(2)=cou(3a),PhB(3b),or DCA(3c)have been synthesised and characterised,including the X-ray crystal structures of complexes 2a,3a,3b and 3c.These complexes exhibit dark stability and have the potential to generate cytotoxic Pt(II)species and free radicals selectively in cancer cells when irradiated.Mono-functionalised complexes 2a-2c showed higher aqueous solubility and more negative reduction potentials.Mono-and di-functionalised complexes displayed higher photocytotoxicity with blue light(1 h,465 nm,4.8 mW cm^(-2))than the parent dihydroxido complex 1(OR_(1)=OR_(2)=OH)in A2780 human ovarian(IC_(50)0.9-2.9μM for 2a-2c;0.11-0.39μM for 3a-3c)and A549 human lung cancer cells(5.4-7.8μM for 2a-2c;1.2-2.6μM for 3a-3c)with satisfactory dark stability.Notably,no apparent dark cytotoxicity was observed in healthy lung MRC-5 fibroblasts for all complexes(IC_(50)>20μM).Significantly higher platinum cellular accumulation and photo-generated ROS levels were observed for the di-functionalised complexes compared with their mono-functionalised analogues when cancer cells were treated under the same concentrations.
基金supported by funds from the Spanish Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación(MCI/AEI/10.13039/501100011033)European Regional Development Fund(FEDER)(projects CTQ2017-84779-R,RTI2018-096891-B-I00,PID2020-117508RB-I00 and RED2018-102471-T)+3 种基金the Generalitat de Catalunya(2017 DI 072)Fundación Séneca-Región de Murcia(project 20857/PI/18)E.O.-F.thanks AECC(PRDMU19003ORTE)G.V.thanks the University of Murcia for a grant(R-1034/2016).
文摘Cyclometalated Ir(III)complexes hold great promise as an alternative to platinum metallodrugs for the therapy and diagnosis of cancer.However,their low aqueous solubility and poor cell membrane permeability are obstacles for in vivo applications.Here we have encapsulated for the first time,using polyurethane–polyurea hybrid nanocapsules(NCs),two phosphorescent tris-cyclometalated Ir(III)complexes incorporating deprotonated 2-arylbenzimidazole ligands,Ir1 and Ir2.Ir(III)-Loaded nanocapsules(NC-Ir1 and NC-Ir2)showed a roughly round shape and controlled particle size distribution around 18 nm.The photophysical properties of aqueous solutions of NCs were similar to those of the free complexes in CH2Cl2,which accounts for the hydrophobic and protective environment generated by the nanoparticles around the cargo.Nanoencapsulation had also a positive effect on the cellular uptake of the metallodrugs and NCs were found to be highly cytotoxic towards several cancer cell lines,whereas Ir(III)complexes alone were found to be inactive.
