https://www.umsl.edu/~chickosj/JSCPUBS/dsccal.pdf

Reference materials for calorimetry and differential thermal analysis

A variety of muscarinic antagonists are currently used as tools to pharmacologically subclassify muscarinic receptors into M1, M2 and M3 subtypes. In the present study, we have determined the affinity profiles of several of these antagonists at five cloned human muscarinic receptors (m1-m5) stably expressed in Chinese hamster ovary cells (CHO-K1). At all five receptors, the (R)-enantiomers of trihexyphenidyl and hexbutinol displayed considerably higher affinities (up to 525-fold) than their corresponding (S)-isomers. The stereoselectivity ratios [inhibition constant(S)/inhibition constant(R)] for both pairs of enantiomers were lowest at m2 receptors, suggesting that less stringent configurational demands are made by this receptor subtype. The "M1-selective" antagonist (R)-trihexyphenidyl displayed high affinities for m1 and m4 receptors. The "M2-selective" antagonists himbacine, (+-)-5,11-dihydro-11- ([(2-[(dipropylamino)methyl]-1- piperidinyl)ethyl)amino]carbonyl)-6H-pyrido(2,3-b)(1,4)benzodiazepine-6- one (AF-DX 384), 11-[4-[4-(diethylamino)butyl]-1-piperidinyl)acetyl)-5,11- dihydro-6H-pyrido(2,3-b) (1,4)benzodiazepine-6-one (AQ-RA 741) and (+)-(11-[2-[(diethylamino) methyl]-1-piperidinyl)acetyl)-5,11-di-hydro-6H-pyrido(2,3-b)(1,4) benzodiazepine-6-one [AF-DX 250; the (+)-enantiomer of AF-DX 116] exhibited high affinities for m2 and m4, intermediate affinities for m1 and m3 and low affinities for m5 receptors. This selectivity profile was most prominent for AQ-RA 741, which displayed 195- and 129-fold higher affinities for m2 and m4 receptors than for m5 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

/pdf/antagonist-binding-profiles-of-five-cloned-human-muscarinic-5751ia4hpc.pdf

Antagonist binding profiles of five cloned human muscarinic receptor subtypes.

Analysis of organic polymorphs. A review

Chemistry challenges in lead optimization: silicon isosteres in drug discovery.

The article contains sections titled: 

1.	Thermal Analysis	
1.1.	General Introduction	
1.1.1.	Definitions	
1.1.2.	Sources of Information	
1.2.	Thermogravimetry	
1.2.1.	Introduction	
1.2.2.	Instrumentation	
1.2.3.	Factors Affecting a TG Curve	
1.2.4.	Applications	
1.3.	Differential Thermal Analysis and Differential Scanning Calorimetry	
1.3.1.	Introduction	
1.3.2.	Instrumentation	
1.3.3.	Applications	
1.3.4.	Modulated-Temperature DSC (MT-DSC)	
1.4.	Simultaneous Techniques	
1.4.1.	Introduction	
1.4.2.	Applications	
1.5.	Evolved Gas Analysis	
1.6.	Mechanical Methods	
1.7.	Less Common Techniques	
2.	Calorimetry	
2.1.	Introduction	
2.2.	Methods of Calorimetry	
2.2.1.	Compensation for Thermal Effects	
2.2.2.	Measurement of a Temperature Difference	
2.2.3.	Temperature Modulation	
2.3.	Calorimeters	
2.3.1.	Static Calorimeters	
2.3.1.1.	Isothermal Calorimeters	
2.3.1.2.	Isoperibolic Calorimeters	
2.3.1.3.	Adiabatic Calorimeters	
2.3.2.	Scanning Calorimeters	
2.3.2.1.	Differential-Temperature Scanning Calorimeters	
2.3.2.2.	Power-Compensated Scanning Calorimeters	
2.3.2.3.	Temperature-Modulated Scanning Calorimeters	
2.3.3.	Chip-Calorimeters	
2.4.	Applications of Calorimetry	
2.4.1.	Determination of Thermodynamic Functions	
2.4.2.	Determination of Heats of Mixing	
2.4.3.	Combustion Calorimetry	
2.4.4.	Reaction Calorimetry	
2.4.5.	Safety Studies	




The article provides an introduction to Thermal Analysis and Calorimetry, methods which are widely used for characterization of materials and compounds with regard to their thermal and chemical properties. The first chapter is devoted to Thermal Analysis (TA). TA has been applied to almost every field of science, with a strong emphasis on solving problems in materials science and engineering, as well as fundamental chemical investigations. The aim of this chapter is to give an overview of the main TA methods and their applications including the respective instrumentation. In the second chapter, the basics of calorimetry are presented. After the introduction of static and dynamic methods to measure heats or heat flow rates, different types of calorimeters are described, both of classical and of modern design. A section on applications of calorimetry in science and technology follows, where some essential fields such as determination of thermodynamic functions and safety studies are presented in more detail.

Thermal Analysis and Calorimetry

The caloric calibration of scanning calorimeters

The temperature calibration of scanning calorimeters: Part 2. Calibration substances

Durch Racematspaltung mit L-(+)- bzw. D-(-)-Weinsaure wurden die Enantiomere des Sila-Procyclidins (R)-1b und (S)-1b erhalten [> 97% ee (NMR), 99.7% ee (DSC)]. Daraus wurden die Hydrochloride (R)-2b und (S)-2b und durch Umsetzung mit CH3I die Enantiomere des Sila-Tricyclamol-iodids (R)-3b und (S)-3b [ > 96% ee (NMR)] hergestellt. Die optisch aktiven Silanole sind in kristalliner Form und in inerten Losungsmitteln konfigurationsstabil, wahrend sie in wasseriger Losung racemisieren (3b schneller als 1b). In Analogie zur Stereoselektivitat der antimuskarinischen Wirkung der Enantiomere der Kohlenstoff-Analoga Procyclidin (1a) und Tricyclamol-iodid (3a) besitzen die (R)-Enantiomere von 1b und 3b eine grosere Affinitat zu den ilealen M2β- und atrialen M2α- Muskarinrezeptoren des Meerschweinchens als die (S)-Antipoden. Alle Silicium-Verbindungen sind starker antimuskarinisch wirksam als ihre Kohlenstoff-Analoga, deren Stereoselektivitat jedoch starker ausgepragt ist. Die Unterschiede in der Affinitat von (R)-1b und (S)-1b zu den ilealen und atrialen Muskarinrezeptoren bestatigen das Konzept der Heterogenitat muskarinischer M2-Rezeptoren (M2α: atrialer Typ; M2β: ilealer Typ).



Sila-Pharmaca, 371). – Preparation and Properties of tbe Enantiomers of the Antimuscarinic Agents Sila-Procyclidine and Sila-Tricyclamol Iodide: optically Active Silanols with Silicon as the Centre of Chirality2)



The enantiomers of sila-procyclidine (R)-1b and (S)-1b [ > 97% ee (NMR), 99.7% ee (DSC)] were obtained by resolution with L-(+)- and D-(-)-tartaric acid, respectively. Starting from (R)-1b and (S)-1b, the hydrochlorides (R)-2b and (S)-2b were prepared and the enantiomers of sila-tricyclamol iodide (R)-3b and (S)-3b [ > 96% ee (NMR)] were synthesized by reaction with CH3I. The optically active silanols show configurational stability in the crystalline state and in inert solvents, whereas they racemize in aqueous solution (3b faster than 1b). By analogy with the stereoselectivity of antimuscarinic action of the enantiomers of the carbon analogues procyclidine (1a) and tricyclamol iodide (3a), the (R) enantiomers of 1b and 3b show a greater affinity for the ileal M2β and atrial M2α muscarinic receptors of the guinea pig than the corresponding (S) antipodes. All silicon compounds exhibit a greater antimuscarinic potency than their carbon analogues, whereas the stereoselectivity of action is more pronounced for the carbon compounds. The differences in affinity for (R)-1b and (S)-1b for ileal and atrial muscarinic receptors confirm the present concept of heterogeneity in muscarinic M2 receptors (M2α: atrial type; M2β: ileal type).

Sila‐Pharmaka, 371) Darstellung und Eigenschaften der Enantiomere der Antimuskarinika Sila‐Procyclidin und Sila‐Tricyclamol‐iodid: Optisch aktive Silanole mit Silicium als Chiralitätszentrum2)

The phase transformation of caffeine: Investigation by dynamic X-ray diffraction and emanation thermal analysis

INTRODUCTION: Calorimetry: Definition, Application Fields and Units Definition of Calorimetry Application Fields for Calorimetry First Example from Life Sciences Second Example from Material Science Third Example from Legal Metrology Units PART I: Fundamentals of Calorimetry METHODS OF CALORIMETRY Compensation of the Thermal Effect Measurement of Temperature Differences Summary of Measuring Principles MEASURING INSTRUMENTS Measurement of Amount of Substance Measurement of Electric Quantities Measurement of Temperatures Chemical Composition FUNDAMENTALS OF THERMODYNAMICS States and Processes Phases and Phase Transitions HEAT TRANSPORT PHENOMENA Heat Conduction Convection Heat Radiation Heat Transfer Entropy Increase during Heat Exchange Conclusions Concerning Calorimetry SURROUNDINGS AND OPERATION CONDITIONS The Isothermal Condition The Isoperibol Condition The Adiabatic Condition The Scanning Condition MEASUREMENT AND EVALUATION Consequences of Temperature Relaxation within the Sample Typical Results from Different Calorimeters Reconstruction of the True Sample Heat Flow Rate from the Measured Function Special Evaluations Determination of the Measurement Uncertainty PART II: Practice of Calorimetry CALORIMETERS Functional Components and Accessories Heating Methods Cooling Methods Comments on Control Systems Thermostats On the Classification of Calorimeters On the Characterization of Calorimeters Isothermal Calorimeters Calorimeters with Heat Exchange between Sample and Surroundings Adiabatic Calorimeters Other Calorimeters RECENT DEVELOPMENTS Microchip Calorimetry Microchip Calorimetry Extreme Ranges of State Calorimetry as an Analytical and Diagnostic Tool CALORIMETRIC MEASUREMENTS: GUIDELINES AND APPLICATIONS General Considerations Guidelines to Calorimetric Measurements Calorimetric Applications Index

Stefan M. Sarge

Papers

The caloric calibration of scanning calorimeters

The temperature calibration of scanning calorimeters: Part 2. Calibration substances

Sila‐Pharmaka, 371) Darstellung und Eigenschaften der Enantiomere der Antimuskarinika Sila‐Procyclidin und Sila‐Tricyclamol‐iodid: Optisch aktive Silanole mit Silicium als Chiralitätszentrum2)

The phase transformation of caffeine: Investigation by dynamic X-ray diffraction and emanation thermal analysis

Calorimetry: Fundamentals, Instrumentation and Applications