scholarly journals Structures of benzoic acids with substituted pyridines and quinolines: salt versus co-crystal formation

CrystEngComm ◽  
2014 ◽  
Vol 16 (26) ◽  
pp. 5802-5810 ◽  
Author(s):  
Gaëlle Ramon ◽  
Kate Davies ◽  
Luigi R. Nassimbeni
Keyword(s):  
Crystal Formation ◽  
Benzoic Acids ◽  
Uncertainty Region ◽  
Salt Versus ◽  
Substituted Pyridines ◽  
Acids And Bases

Acids and bases were crystallized so that their ΔpKa spans the ‘uncertainty’ region for the formation of salt versus co-crystals.

scholarly journals 'Uncertainty' region of acid-base ΔpKa: Salt versus co-crystal formation

2014 ◽  
Vol 70 (a1) ◽  
pp. C558-C558
Author(s):  
Gaelle Ramon ◽  
Kate Davies ◽  
Luigi Nassimbeni
Keyword(s):  
Hydrogen Bond ◽  
Crystal Engineering ◽  
General Rule ◽  
Ph Control ◽  
Crystal Formation ◽  
Acid Base ◽  
Uncertainty Region ◽  
Salt Versus ◽  
Substituted Pyridines ◽  
Substituted Benzoic Acids

The hydrogen bond is a very important interaction which demonstrates a wide variety in strength and shape and can be held as the central point in the crystal engineering process of a great number of compounds. In the formation of salts versus co-crystals, pH control is necessary in order to obtain one form or the other. In the pharmaceutical industry which is actively developing Active Pharmaceutical Ingredients (APIs) with desirable properties, such consideration is of major concern. In 2012, Cruz-Cabeza[1] carried out a survey of over 6 000 structures and found a linear relationship between ΔpKa and the probability of proton transfer for the pKa range of -1 to +4. The cross-over point was determined to be at ΔpKa = 1.3. Beyond this point the probability to obtain a salt rather than a co-crystal is higher than 50%. Parallel to this work, Gilli & Gilli[2] have built a sliding rule which predicts the strength of a Donor – Acceptor hydrogen bond based on the ΔpKa of the system. Their device predicts the formation of salts if ΔpKa > 3, and co-crystals when ΔpKa < -3. In their paper, Gilli & Gilli point out that the interval of ΔpKa matching should be shifted by 1.5 units when interpreting crystal structures,[3] which agrees with the findings of Cruz-Cabeza. In this work we discuss the bonding of 22 structures made up of acid-base pairs which either form salts or co-crystals. A series of five substituted benzoic acids with 10 substituted pyridines and quinolines have been crystallized so that their ΔpKa, defined as pKa(base) – pKa(acid), spans the range -1.14 to +4.16. This covers the `uncertainty' region for the formation of salt versus co-crystals. Although most of our results confirmed that structure formation of co-crystal versus salt parts at ΔpKa ≍ 2, we report here a structure that does not follow the general rule and serves as a cautionary tale.

A STUDY OF MIXED LIQUID CRYSTAL FORMATION IN MIXTURE OF p-METHOXY AND p-ETHOXY BENZOIC ACIDS

1975 ◽  
Vol 36 (C1) ◽  
pp. C1-399-C1-401 ◽  
Author(s):  
J. M. LOHAR
Keyword(s):  
Liquid Crystal ◽  
Crystal Formation ◽  
Benzoic Acids

scholarly journals Multicomponent crystal formation of baclofen with acids and bases

2019 ◽  
Vol 75 (a2) ◽  
pp. e591-e591
Author(s):  
Ramokone Malapile ◽  
Luigi Nassimbeni ◽  
Nikoletta Bathori
Keyword(s):  
Crystal Formation ◽  
Acids And Bases

Solvent effect on preferred protonation sites in nicotinate and isonicotinate anions

1996 ◽  
Vol 74 (4) ◽  
pp. 613-620 ◽  
Author(s):  
Jean-Claude Hallé ◽  
Jacques Lelievre ◽  
François Terrier
Keyword(s):  
Dimethyl Sulfoxide ◽  
Molecular Form ◽  
Tautomeric Equilibrium ◽  
Benzoic Acids ◽  
Acidity Constants ◽  
Pyridinium Ring ◽  
Substituted Pyridines ◽  
Complete Ionization ◽  
Ionization Scheme ◽  
Pyridinium Cations

Potentiometric determinations of the two successive acidities of nicotinic and isonicotinic acids (AH2+) have been carried out in aqueous dimethyl sulfoxide mixtures containing up to 95% Me2SO by volume. In both systems, the results reveal that the addition of Me2SO induces a proton transfer from the pyridinium ring to the carboxylate group, the tautomeric equilibrium between the neutral forms of the two acids being displaced toward the zwitterionic form (AH±) in aqueous solution, but toward the molecular form (AH°) in Me2SO. An analysis of the data by means of Hammett relationships previously established for benzoic acids over the whole range of H2O/Me2SO mixtures allowed the four microscopic acidity constants as well as the tautomeric equilibrium constant KT pertaining to the complete ionization scheme of the two acids to be determined. At 20 °C, there are equal populations of the tautomeric AH° and AH± species in the mixtures containing 38 and 47% Me2SO for the nicotinic and isonicotinic systems, respectively. Hammett relationships describing the ionization behaviour of a number of substituted pyridinium cations in H2O/Me2SO mixtures are also discussed. Possible reasons accounting for the peculiar effects exerted by the NH2, CONH2, and COOH substituents on the process are suggested. Key words: nicotinic and isonicotinic acids, substituted pyridines, acidities, tautomeric equilibrium, protonation sites, water – dimethyl sulfoxide mixtures.

The Critical Point Drying Method Applied to Scanning Electron Microscopy of L-929 Cells

1970 ◽  
Vol 28 ◽  
pp. 278-279
Author(s):  
Charles TurnbiLL ◽  
Delbert E. Philpott
Keyword(s):  
Electron Microscopy ◽  
Carbon Dioxide ◽  
Surface Tension ◽  
Critical Point ◽  
Freeze Drying ◽  
Attractive Alternative ◽  
Crystal Formation ◽  
Critical Point Drying ◽  
Time Required ◽  
Scanning Electron

The advent of the scanning electron microscope (SCEM) has renewed interest in preparing specimens by avoiding the forces of surface tension. The present method of freeze drying by Boyde and Barger (1969) and Small and Marszalek (1969) does prevent surface tension but ice crystal formation and time required for pumping out the specimen to dryness has discouraged us. We believe an attractive alternative to freeze drying is the critical point method originated by Anderson (1951; for electron microscopy. He avoided surface tension effects during drying by first exchanging the specimen water with alcohol, amy L acetate and then with carbon dioxide. He then selected a specific temperature (36.5°C) and pressure (72 Atm.) at which carbon dioxide would pass from the liquid to the gaseous phase without the effect of surface tension This combination of temperature and, pressure is known as the "critical point" of the Liquid.

Techniques for cryoultramicrotomy of propane jet frozen biological samples

1986 ◽  
Vol 44 ◽  
pp. 260-261
Author(s):  
B. Craig ◽  
L. Hawkey ◽  
A. LeFurgey
Keyword(s):  
Freeze Fracture ◽  
Freeze Substitution ◽  
Heart Cells ◽  
Crystal Formation ◽  
X Ray ◽  
Transmission Electron ◽  
Scanning Transmission ◽  
Chick Heart ◽  
Embryonic Chick Heart ◽  
A New Technique

Ultra-rapid freezing followed by cryoultramicrotomy is essential for the preservation of diffusible elements in situ within cells prior to scanning transmission electron microscopy and quantitative energy dispersive x-ray microanalysis. For cells or tissue fragments in suspension and for monolayer cell cultures, propane jet freezing provides cooling rates greater than 30,000°C/sec with regions up to 40μm in thickness free of significant ice crystal formation. While this method of freezing has frequently been applied prior to freeze fracture or freeze substitution, it has not been widely utilized prior to cryoultramicrotomy and subsequent x-ray microanalytical studies. This report describes methods devised in our laboratory for cryosectioning of propane jet frozen kidney proximal tubule suspensions and cultured embryonic chick heart cells, in particular a new technique for mounting frozen suspension specimens for sectioning. The techniques utilize the same specimen supports and sample holders as those used for freeze fracture and freeze substitution and should be generally applicable to any cell suspension or culture preparation.

High-pressure freezing and freeze substitution of plant tissue

1992 ◽  
Vol 50 (1) ◽  
pp. 748-749
Author(s):  
William P. Sharp ◽  
Robert W. Roberson
Keyword(s):  
High Pressure ◽  
Cell Structure ◽  
Leaf Tissue ◽  
Freeze Substitution ◽  
Crystal Formation ◽  
Ice Crystal ◽  
High Pressure Freezing ◽  
Cell Components ◽  
Cold Metal ◽  
Brome Grass

The aim of ultrastructural investigation is to analyze cell architecture and relate a functional role(s) to cell components. It is known that aqueous chemical fixation requires seconds to minutes to penetrate and stabilize cell structure which may result in structural artifacts. The use of ultralow temperatures to fix and prepare specimens, however, leads to a much improved preservation of the cell’s living state. A critical limitation of conventional cryofixation methods (i.e., propane-jet freezing, cold-metal slamming, plunge-freezing) is that only a 10 to 40 μm thick surface layer of cells can be frozen without distorting ice crystal formation. This problem can be allayed by freezing samples under about 2100 bar of hydrostatic pressure which suppresses the formation of ice nuclei and their rate of growth. Thus, 0.6 mm thick samples with a total volume of 1 mm3 can be frozen without ice crystal damage. The purpose of this study is to describe the cellular details and identify potential artifacts in root tissue of barley (Hordeum vulgari L.) and leaf tissue of brome grass (Bromus mollis L.) fixed and prepared by high-pressure freezing (HPF) and freeze substitution (FS) techniques.

The “KIMWIPE” Effect in Ultra-Thin Cryosections

1985 ◽  
Vol 43 ◽  
pp. 458-459
Author(s):  
I. Taylor ◽  
P. Ingram ◽  
J.R. Sommer
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Muscle Fibers ◽  
Ice Crystals ◽  
Crystal Formation ◽  
Ice Crystal ◽  
Thin Sections ◽  
Skeletal Muscle Fibers ◽  
Freeze Dried ◽  
Ice Crystal Formation

In studying quick-frozen single intact skeletal muscle fibers for structural and microchemical alterations that occur milliseconds, and fractions thereof, after electrical stimulation, we have developed a method to compare, directly, ice crystal formation in freeze-substituted thin sections adjacent to all, and beneath the last, freeze-dried cryosections. We have observed images in the cryosections that to our knowledge have not been published heretofore (Figs.1-4). The main features are that isolated, sometimes large regions of the sections appear hazy and have much less contrast than adjacent regions. Sometimes within the hazy regions there are smaller areas that appear crinkled and have much more contrast. We have also observed that while the hazy areas remain still, the regions of higher contrast visibly contract in the beam, often causing tears in the sections that are clearly not caused by ice crystals (Fig.3, arrows).

HREM observation of NiO growth on submicron spheres of pure nickel

1989 ◽  
Vol 47 ◽  
pp. 548-549
Author(s):  
C.M. Teng ◽  
T.F. Kelly ◽  
J.P. Zhang ◽  
H.M. Lin ◽  
Y.W. Kim
Keyword(s):  
Nickel Oxide ◽  
Grain Boundaries ◽  
Pure Nickel ◽  
Submicron Particles ◽  
Crystal Formation ◽  
Nickel Wire ◽  
Liquid Droplets ◽  
Oxide Interface ◽  
Nickel Chromium ◽  
Chromium Alloys

Spherical submicron particles of materials produced by electrohydrodynamic (EHD) atomization have been used to study a variety of materials processes including nucleation of alternative crystallization phases in iron-nickel and nickel-chromium alloys, amorphous solidification in submicron droplets of pure metals, and quasi-crystal formation in nickel-chromium alloys. Some experiments on pure nickel, nickel oxide single crystals, the nickel/nickel(II) oxide interface, and grain boundaries in nickel monoxide have been performed by STEM. For these latter studies, HREM is the most direct approach to obtain particle crystal structures at the atomic level. Grain boundaries in nickel oxide have also been investigated by HREM. In this paper, we present preliminary results of HREM observations of NiO growth on submicron spheres of pure nickel.Small particles of pure nickel were prepared by EHD atomization. For the study of pure nickel, 0.5 mm diameter pure nickel wire (99.9975%) is sprayed directly in the EHD process. The liquid droplets solidify in free-flight through a vacuum chamber operated at about 10-7 torr.

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