13 research outputs found
Experimental Determination of Pseudorotation Potentials for Disubstituted Cyclopentanes Based on Spin–Spin Coupling Constants
trans-1,2-dibromocyclopentane was performed with use of our total lineshape fitting algorithm VALISA. The resulting high precision spin-spin coupling constants were then applied to the problem of conformational analysis, yielding a continuos potential of pseudorotation for the studied compounds in CDCl3, CCl4, and CD3CN solutions
pH-Triggered conformational switches based on trans-2-aminocyclohexanol moiety
Properly designed trans-2-aminocyclohexanols possess a negative allosteric cooperativity and can serve as powerful conformational pH-triggers. Their protonation leads to a conformational flip due to a strong intramolecular hydrogen bond. This \u27impulse\u27 is mechanically transmitted by the cycle to induce a conformational change of a remote site, thus altering its properties. Variation of NR2 groups allows a tuning of the conformational equilibrium, which was studied by NMR. These triggers were used in pH-sensitive lipid vesicles for drug and gene delivery
pH-Triggered conformational switches based on trans-2-aminocyclohexanol moiety
Properly designed trans-2-aminocyclohexanols possess a negative allosteric cooperativity and can serve as powerful conformational pH-triggers. Their protonation leads to a conformational flip due to a strong intramolecular hydrogen bond. This \u27impulse\u27 is mechanically transmitted by the cycle to induce a conformational change of a remote site, thus altering its properties. Variation of NR2 groups allows a tuning of the conformational equilibrium, which was studied by NMR. These triggers were used in pH-sensitive lipid vesicles for drug and gene delivery
pH-Triggered conformational switches based on trans-2-aminocyclohexanol moiety
Properly designed trans-2-aminocyclohexanols possess a negative allosteric cooperativity and can serve as powerful conformational pH-triggers. Their protonation leads to a conformational flip due to a strong intramolecular hydrogen bond. This \u27impulse\u27 is mechanically transmitted by the cycle to induce a conformational change of a remote site, thus altering its properties. Variation of NR2 groups allows a tuning of the conformational equilibrium, which was studied by NMR. These triggers were used in pH-sensitive lipid vesicles for drug and gene delivery
Fliposomes: pH-controlled release from liposomes containing new trans-2-morpholinocyclohexanol-based amphiphiles that perform a conformational flip and trigger an instant cargo release upon acidification
A new type of pH-sensitive liposome (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in the areas of increased acidity. The flipids (1-3) are equipped with a trans-2-morpholinocyclohexanol conformational switch. pH-Sensitive flipsomoes containing one of these flipids, POPC, and PEG-ceramide (molar ratio 50/45/4) were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX demonstrated an unusually quick content release (in a few seconds) at pH below 5.5 which was more efficient in the case of flipid 1 with the shorter linear c12-tails. The pH-titration curve for the flipsomoe leakage paralleled the curve for the acid-induced conformational flip of 1-3 studied by
Fliposomes: pH-controlled release from liposomes containing new trans-2-morpholinocyclohexanol-based amphiphiles that perform a conformational flip and trigger an instant cargo release upon acidification
A new type of pH-sensitive liposome (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in the areas of increased acidity. The flipids (1-3) are equipped with a trans-2-morpholinocyclohexanol conformational switch. pH-Sensitive flipsomoes containing one of these flipids, POPC, and PEG-ceramide (molar ratio 50/45/4) were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX demonstrated an unusually quick content release (in a few seconds) at pH below 5.5 which was more efficient in the case of flipid 1 with the shorter linear c12-tails. The pH-titration curve for the flipsomoe leakage paralleled the curve for the acid-induced conformational flip of 1-3 studied by
pH-Triggered conformational switches based on trans-2-aminocyclohexanol moiety
Properly designed trans-2-aminocyclohexanols possess a negative allosteric cooperativity and can serve as powerful conformational pH-triggers. Their protonation leads to a conformational flip due to a strong intramolecular hydrogen bond. This \u27impulse\u27 is mechanically transmitted by the cycle to induce a conformational change of a remote site, thus altering its properties. Variation of NR2 groups allows a tuning of the conformational equilibrium, which was studied by NMR. These triggers were used in pH-sensitive lipid vesicles for drug and gene delivery
Solvent effects on C=O stretching frequencies of some 1-substituted 2-pyrrolidinones
In an effort to model solute–solvent interactions, the C=O stretching frequencies of five 1-substituted 2-pyrrolidinones and four other carbonyl-containing compounds were measured for 30 common solvents. These were then correlated with four empirical parameter sets and one theoretical (computational) parameter set. While an empirical parameter set gave the best correlation equations, the theoretical parameter equations are physically and statistically significant. Solvent volume, polarizability and hydrogen bond donor acidity (capacity) terms are significant in the correlation equations.
Selective, Metal-Free Approach to 3- or 5‑CF<sub>3</sub>‑Pyrazoles: Solvent Switchable Reaction of CF<sub>3</sub>‑Ynones with Hydrazines
A detailed study
of the reaction of trifluoroacetylated acetylenes
and aryl (alkyl) hydrazines was performed, aimed to the regioselective
synthesis of 3- or 5-trifluoromethylated pyrazoles. It was found that
the regioselectivity of reaction depends dramatically on the solvent
nature. Highly polar protic solvents (hexafluoroisopropanol) favor
the formation of 3-trifluoromethylpyrazoles. In contrast, when the
reaction was performed in polar aprotic solvents (DMSO), the formation
of their 5-CF<sub>3</sub>-substituted isomers was preferentially observed.
Alternatively, the regioselective assembly of 3-CF<sub>3</sub>-substituted
pyrazoles can be performed via two-step one-pot procedure. The reaction
of trifluoromethylated ynones with aryl (alkyl) hydrazines in the
presence of acidic catalysts leads to formation of the corresponding
hydrazones. The latter can be smoothly transformed into 3-CF<sub>3</sub>-pyrazoles by treatment with a base. This solvent-switchable procedure
was used for the preparation of such important drugs as Celebrex and <b>SC-560</b> as well as their isomers in gram scale. The possible
reaction mechanism is discussed