Basicity of 1,8-bis(dimethylamino)naphthalene and 1,4-diazabicyclo[2.2.2]octane in water and dimethylsulfoxide

1987 ◽  
Vol 65 (5) ◽  
pp. 996-1001 ◽  
Author(s):  
Robert L. Benoit ◽  
Diane Lefebvre ◽  
Monique Fréchette
Keyword(s):  
Free Energy ◽  
Partition Coefficients ◽  
Enthalpy Of Solution ◽  
Ionization Constants ◽  
Base System ◽  
Proton Sponge ◽  
Acid Base ◽  
Enthalpy Of Transfer ◽  
Calculated Enthalpy ◽  
Base Strength

The ionization constants of the conjugate acids [Formula: see text] of two bases widely used in synthesis, 1,8-bis(dimethylamino)naphthalene (PS), and 1,4-diazabicyclo[2.2.2]octane (DABCO), have been obtained in Me2SO and water. The partition coefficients of both bases B and their heats of solution and protonation have also been determined. The basicity of PS is dramatically reduced when passing from water to Me2SO while the basicity of DABCO remains unchanged, thus making DABCO the stronger base in Me2SO. The solvent effect on the base strength is analyzed in terms of free energy and enthalpy of transfer for B and H+, and for BH+, from water to Me2SO. The entropy-controlled much stronger solvation of PS in Me2SO is in line with that of aromatic compounds while the increased solvation of DABCO in water is due to H-bonding of its two nitrogens. PSH+, like H+, is better solvated by Me2SO while DABCOH+ does not show a definite preference for one solvent. The calculated enthalpy of solution of gaseous PSH+ is abnormally low when compared to that of DABCOH+ and of related BH+ ions, thus indicating that the proton of PSH+, in a strong intramolecular H-bond, does not normally H-bond to the solvent. Our results suggest that the proton sponge acid-base system could be used as a convenient reference to determine the free energy and enthalpy of transfer of H+ between solvents.

scholarly journals 2,6-Di-tert-butylpyridine: an unusually weak base in dimethylsulfoxide

1988 ◽  
Vol 66 (5) ◽  
pp. 1159-1162 ◽  
Author(s):  
Robert L. Benoit ◽  
Monique Fréchette ◽  
Diane Lefebvre
Keyword(s):  
Gas Phase ◽  
Partition Coefficients ◽  
Enthalpy Of Solution ◽  
Solvent Molecule ◽  
Ionization Constants ◽  
Enthalpies Of Solution ◽  
Weak Base ◽  
High Basicity ◽  
Transfer Parameters ◽  
Sterically Hindered

The ionization constants of the conjugate acids BH+ of pyridine, 2-picoline, 2,6-lutidine, and 2,6-di-tert-butylpyridine (DTBP) have been determined in Me2SO. The partition coefficients of the bases B between Me2SO and water, and the enthalpies of solution and protonation of B in Me2SO have also been obtained. In contrast to its high basicity in the gas phase, DTBP is an abnormally weak base in Me2SO (pK = 0.81). The factors responsible for this very low basicity are analyzed by considering correlations between the gas-phase, Me2SO, and aqueous basicities of B and by comparing the transfer parameters for B and BH+. The solvation of DTBP and DTBPH+ in Me2SO and in water differs. While the solvation of DTBP in Me2SO is normal, the enthalpy of solution of DTBPH+ in Me2SO is abnormally low and close to that of a cation whose solvation is nonspecific. This suggests a much reduced H-bonding between sterically hindered DTBPH+ and the large Me2SO solvent molecule.

A molecular dynamics study on liquid 1-octanol. Part 3. Evaluating octanol/water partition coefficients of novel thrombin inhibitors via free-energy perturbations

2005 ◽  
Vol 102 (5) ◽  
pp. 542-553 ◽  
Author(s):  
César Augusto Fernandes De Oliveira ◽  
Cristiano Ruch Werneck Guimarães ◽  
Heloisa De Mello ◽  
Aurea Echevarria ◽  
Ricardo Bicca De Alencastro
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Partition Coefficients ◽  
Thrombin Inhibitors ◽  
Free Energy Perturbations

scholarly journals Evaluation of log P, pKa, and log D predictions from the SAMPL7 blind challenge

2021 ◽  
Author(s):  
Teresa Danielle Bergazin ◽  
Nicolas Tielker ◽  
Yingying Zhang ◽  
Junjun Mao ◽  
M. R. Gunner ◽  
...  
Keyword(s):  
Free Energy ◽  
Partition Coefficients ◽  
Physical Property ◽  
Rational Drug Design ◽  
Log P ◽  
Prediction Methods ◽  
Research Groups ◽  
Reasonable Accuracy ◽  
Statistical Assessment ◽  
Rational Drug

AbstractThe Statistical Assessment of Modeling of Proteins and Ligands (SAMPL) challenges focuses the computational modeling community on areas in need of improvement for rational drug design. The SAMPL7 physical property challenge dealt with prediction of octanol-water partition coefficients and pKa for 22 compounds. The dataset was composed of a series of N-acylsulfonamides and related bioisosteres. 17 research groups participated in the log P challenge, submitting 33 blind submissions total. For the pKa challenge, 7 different groups participated, submitting 9 blind submissions in total. Overall, the accuracy of octanol-water log P predictions in the SAMPL7 challenge was lower than octanol-water log P predictions in SAMPL6, likely due to a more diverse dataset. Compared to the SAMPL6 pKa challenge, accuracy remains unchanged in SAMPL7. Interestingly, here, though macroscopic pKa values were often predicted with reasonable accuracy, there was dramatically more disagreement among participants as to which microscopic transitions produced these values (with methods often disagreeing even as to the sign of the free energy change associated with certain transitions), indicating far more work needs to be done on pKa prediction methods.

Correlation of Human and Animal Air-to-Blood Partition Coefficients With a Single Linear Free Energy Relationship Model

2008 ◽  
Vol 27 (9) ◽  
pp. 1130-1139 ◽  
Author(s):  
Laura M. Sprunger ◽  
Jennifer Gibbs ◽  
William E. Acree ◽  
Michael H. Abraham
Keyword(s):  
Free Energy ◽  
Partition Coefficients ◽  
Linear Free Energy Relationship ◽  
Linear Free Energy ◽  
Relationship Model

Acids and Bases. Solvent Effects on Acid-Base Strength. By Brian G. Cox.

2013 ◽  
Vol 52 (30) ◽  
pp. 7638-7638 ◽  
Author(s):  
Robin A. Cox
Keyword(s):  
Solvent Effects ◽  
Acid Base ◽  
Base Strength ◽  
Acids And Bases

The influence of dissolved organic matter on the acid–base system of the Baltic Sea

2014 ◽  
Vol 132 ◽  
pp. 106-115 ◽  
Author(s):  
Karol Kuliński ◽  
Bernd Schneider ◽  
Karoline Hammer ◽  
Ulrike Machulik ◽  
Detlef Schulz-Bull
Keyword(s):  
Organic Matter ◽  
Dissolved Organic Matter ◽  
Baltic Sea ◽  
Base System ◽  
The Baltic Sea ◽  
Acid Base ◽  
The Baltic

Micro-electromembrane extraction using multiple free liquid membranes and acceptor solutions – Towards selective extractions of analytes based on their acid-base strength

2016 ◽  
Vol 943 ◽  
pp. 64-73 ◽  
Author(s):  
Pavel Kubáň ◽  
Knut Fredrik Seip ◽  
Astrid Gjelstad ◽  
Stig Pedersen-Bjergaard
Keyword(s):  
Liquid Membranes ◽  
Acid Base ◽  
Base Strength ◽  
Electromembrane Extraction

scholarly journals SPECIFIC NATURE OF ACID-BASE INTERACTION OF OCTA(4-TERT-BUTYLPHENYL)TETRAPYRAZINOPORPHYRAZINE WITH ORGANIC PROTON-ACCEPTOR MOLECULES IN BENZENE

2021 ◽  
Vol 64 (3) ◽  
pp. 33-40
Author(s):  
Oleg A. Petrov ◽  
Aleksandr S. Semeykin ◽  
Mariya V. Shilovskaya ◽  
Tatiana V. Lyubimova
Keyword(s):  
Proton Transfer ◽  
Proton Acceptor ◽  
Base System ◽  
Excess Charge ◽  
Hydrogen Atoms ◽  
Acid Base ◽  
Base Interaction ◽  
Base Equilibrium ◽  
Acid Base Equilibrium ◽  
Acid Base Interaction

The reaction of acid-base interaction of octa(4-tert-butylphenyl)tetrapyrazinophosphyrazine with pyridine, 2-methylpyridine, morhpoline, pipyridine, n-butylamine, tert-butylamine, diethylamine, triethylamine and dimethylsulfoxide in benzene was investigated. It is shown that the researched porphyrazine forms kinetically stable proton transfer complexes with pyridine, 2-methylpyridine, morpholine and dimethylsulfoxide. In benzene-base system an acid-base equilibrium between the molecular form of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine and its proton transfer complex was established. The interaction of substituted tetrapyrazinoporphyrazine with morpholine in benzene was revealed to be a kinetically controllable process which occurs with low reaction rate and high values of activation energy. Such values are not inherent to most of relatively simple liquid-phase acid-base systems. The kinetic equation of the process was found, and, based on the spectral changes accompanying the reaction, a cheme of two-stage process of proton transfer of NH-groups of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine to morpholine in benzene was proposed. A possible structure of proton transfer complex of octa(4-tert-butylphenyl)tetrapyrazinoporphyrazine with organic bases is shown. In these complexes the inner hydrogen atoms of the cycle, bonded with base molecules, lie under and above the plane of the molecule, and the proton transfer from acid to base is limited either by the H-complex or the ion-ion associates constituting an H-bonded ion pair. Depending on the proton accepting tendency of the base, the acid-base equilibrium can shift towards or away from the more or less polarized structure. It was revealed that in benzene - n-butylamine (tri-butylamine, diethylamine, triethylamine, pipyridine) system the acid-base interaction involving octa(4- tert-butylphenyl)tetrapyrazinoporphyrazine occurs incredibly fast, with rates not measurable by standard spectrophotography methods. The forming proton transfer complexes are highly labile due to concurrent proton reaction occurring, leading to the formation of dianion form of octa(4- tert-butylphenyl)tetrapyrazinoporphyrazine. This form undergoes spontaneous dissolution into low-molecular colorless products due to the lack of compensation of excess charge in the macrocycle.

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