Compound Ionization Properties

Acids consistently display low solubility in DMSO. In our Pfizer studies we found acids to be 4 times more likely to have poor DMSO solubility of less than 5pgmL than any other functionality. The reason is that DMSO with its very electronegative oxygens is a poor solvator for any compound with partial negative or full anionic character. 

---

Quinoxalines are weakly basic the basicities of quinoxaline derivatives were determined potentiometrically and of 5,6-substituted 2,3-dimethylquinoxalines either spectrophotometri-cally, or by potentiometric titration. Quinoxaline has a melting point of 29-30 C, a boiling point of 108-111 °C/12 Torr, and 0.56 (— 5.52) quinoxaline 1-oxide has a pK of 0.25 and is, therefore, a weaker base than the parent compound.Ionization properties (e.g., ionization constants) show that quinoxaline is a relatively weak base. Quinoxaline has a dipole moment of 0.51 D in benzene." Polarographic studies were performed on quinoxalines," and electrochemical and spectroscopic characterization of, V,A -dialkylquinoxalinium salts has been reported. ... 

Quinoxalin-2-ones are in tautomeric equilibrium with 2-hydroxy-quinoxalines, but physical measurements indicate that both in solution and in the solid state they exist as cyclic amides rather than as hydroxy compounds. Thus quinoxalin-2-one and its A -methyl derivative show practically identical ultraviolet absorption and are bases of similar strength. In contrast, the ultraviolet spectra of quinoxalin-2-one and its 0-methyl derivative (2-methoxyquinoxaIine) are dissimilar. The methoxy compound is also a significantly stronger base (Table II). Similar relationships also exist between the ultraviolet absorption and ionization properties of 3-methylquinoxalin-2-one and its N- and 0-methyl derivatives. The infrared spectrum of 3- (p-methoxy-benzyl)quinoxalin-2-one (77) in methylene chloride shows bands at 3375 and 1565 cm" which are absent in the spectrum of the deuterated... 

According to the electrostatic model the solvation is due to electrostatic interaction between the charged ions and the dipolar solvent molecules. Thus the solvating and ionizing properties of a solvent are considered as being due primarily to the dipole moment of the solvent molecules. Thus, ionic compounds such as sodium chloride are insoluble in non-polar solvents such as carbon tetrachloride. Actually, rather than the dipole moment the field action of the dipoles should be considered. This approach might explain why acetonitrile (p = 3.2) is poor in its ionizing properties compared to water (p = 1.84). However, no numerical values are available for this quantity. 

The general method for ASMS is shown in Fig. 4.1. In ASMS, the target concentration is generally set at 5-10 xM, so that at equilibrium, ligands with affinities of no weaker than Ku 10 xM will be significantly bound and, therefore, retained in the ultrafiltration steps. The minimal concentration of each small molecule is dictated by the eventual need to detect ligands by mass spectrometry after several cycles of ultrafiltration and subsequent extraction. In order to ensure detection just above baseline for the vast majority of compounds, which vary in inherent ionization properties and efficiency of mass spectrometric visibility, the starting compound concentration is set at 1.5 pM per compound. The mixture... 

Unfortunately, for the majority of small molecule LC-MS/MS analyses, stable isotope labelled internal standards are not available so far. In such cases, compounds with a very similar molecular structure typically serve as internal standard ( homologues or analogues ). Since the ionization properties are substantially determined by functional groups of a molecule, ionization behaviour may differ significantly—even between compounds with very similar over-all molecular structure. Differential clustering, e.g. with sodium, ammonium or formate ions often present in mobile phases may as well impact the parity of ionization yield between analyte and internal standard. Hence the availability of an appropriate homologue is crucial and critical for the development of reliable LC-MS/MS methods in TDM [51]. 

Despite the high cost of the equipment required and the time taken for sample preparation and spectra acquisition, MAS-HR NMR provides invaluable stmctural information about the species present in a reaction. Only a few milligrams of resin beads are required and they can be recovered as the technique is nondestructive. The complementarity of the technique with other analytical methods is clear MALDl-TOP cannot discriminate among compounds with the same MW and depends on the ionization properties of the resin-bound compound, while PTIR depends on the presence of selected functional groups in the molecule. MAS-HR NMR can be used independently from the nature of the performed reaction and the functional groups formed or lost during the SPS step. Additionally, two-dimensional MAS techniques such as 2D-COSY (correlated spectroscopy) and TOCSY (total correlated spectroscopy) (171) or 2D-SECSY (spin echo correlation spectroscopy) (181) can provide more detailed information that may be useful in specific cases. 

This article describes recent advances in the experimental determination of electron impact ionization cross sections for silane (SiH4) its radicals, SiH. (x = 1 to 3) and the Si-organic molecules tetramethylsilane (TMS), Si(CH3)4 tetraethoxysilane (TEOS), Si(0-CH2-CH3)4 and hexamethyldisiloxane (HMDSO), (CH3)3-Si-0-Si-(CH3)3, which is one of the simplest siloxane compounds. These are model substances, and the results obtained for these species may be used in efforts to predict the ionization properties of other, more complex Si-organic molecules. The ionization cross sections of the stable compounds were measured using a high-resolution double-focusing mass spectrometer. The cross-section data for the radicals were obtained in a fast-neutral-beam apparatus. 

Due to their good donor properties formamide and acetamide dissolve many ionic compounds7 94,96 g ch as alkali halides, various salts of copper, zinc, cadmium, aluminium, tin, lead, nickel, mercury and other acceptor compounds, such as FeCls or SbCls. The high dielectric constants allow considerable dissociation of the compounds ionized in the solutions. 

Complex fluorides are easily prepared by making use of both the fluorinating and ionizing properties of bromine (III) fluoride. Compounds which will yield the acidic and basic fluorides by fluorination are mixed and allowed to react with excess bromine (III) fluoride. A mixture of equivalent amounts of potassium chloride and antimony (III) fluoride, for example, may be used to obtain potassium... 

Up to this point, the detection Unfit and sensitivity comparisons of the different sources have focused primarily on compoimds that ionize efficiently with all the techniques. It is important to understand the coverage or scope of an ionization technique across the chemical space of general interest, particularly when confronted with unknown compounds, or compounds whose structures are known but whose ionization properties have not been tested, and there is no time to assess a variety of options. This situation occurs in many drug discovery laboratories measuring in vitro ADME properties (administration, distribution, metabolism, excretion) where many different chemical species need to be assayed quickly. The data used to generate the relative efficiency values within a source in Tables 1-3 were used to calculate the relative MRM efficiency between the three sources and are shown in Table 13.4. The MALDI data were acquired in the most practical fashion to obtain a quantitative measurement where only a small percentage of the sample spot was ablated with a single raster. The ESI and APCI data were obtained by flow injection analysis at 200 and lOOOpL/min, respectively. Electrospray is the most sensitive ion source in nearly all... 

---