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The phenomenon of ion mobility (IM), the movement/transport of charged particles under the influence of an electric field, was first observed in the early 20th Century and harnessed later in ion mobility spectrometry (IMS). There have been rapid advances in instrumental design, experimental methods, and theory together with contributions from computational chemistry and gas‐phase ion chemistry, which have diversified the range of potential applications of contemporary IMS techniques. Whilst IMS‐mass spectrometry (IMS‐MS) has recently been recognized for having significant research/applied industrial potential and encompasses multi‐/cross‐disciplinary areas of science, the applications and impact from decades of research are only now beginning to be utilized for “small molecule” species. This review focuses on the application of IMS‐MS to “small molecule” species typically used in drug discovery (100–500 Da) including an assessment of the limitations and possibilities of the technique. Potential future developments in instrumental design, experimental methods, and applications are addressed. The typical application of IMS‐MS in relation to small molecules has been to separate species in fairly uniform molecular classes such as mixture analysis, including metabolites. Separation of similar species has historically been challenging using IMS as the resolving power, R, has been low (3–100) and the differences in collision cross‐sections that could be measured have been relatively small, so instrument and method development has often focused on increasing resolving power. However, IMS‐MS has a range of other potential applications that are examined in this review where it displays unique advantages, including: determination of small molecule structure from drift time, “small molecule” separation in achiral and chiral mixtures, improvement in selectivity, identification of carbohydrate isomers, metabonomics, and for understanding the size and shape of small molecules. This review provides a broad but selective overview of current literature, concentrating on IMS‐MS, not solely IMS, and small molecule applications. © 2012 Wiley Periodicals, Inc., Mass Spec Rev 32:43–71, 2013

Aqueous colloidal microgels have been prepared, based on poly(N-isopropylacrylamide) [poly(NIPAM)], cross-linked with bisacrylamide, containing 5% w/w acrylic acid (AAc) as a comonomer. Transmission electron micrographs of the microgels show that the copolymer microgels are monodisperse spheres. The size of the microgel particles containing 5% AAc has been studied, using dynamic light scattering, as a function of pH (3-lo), ionic strength (10-4-10-' M NaC1) and temperature (20-75°C). The hydrodynamic diameter of the copolymer microgels decrease both with increasing ionic strength (at pH 6 and 25°C) and reversibly with increasing temperature at pH values of 2.6, 3.4 and 6.5. However, under isothermal conditions in M NaCl at 25 "C, the hydrodynamic diameter increases in going from pH 3.3-9.4. In addition, the temperature-induced conformational changes in the polymer chains have been followed using high-sensitivity differential scanning calorimetry (HSDSC). A comparison is made with the behaviour of poly(N1PAM) microgel particles, not containing AAc. Explanations are offered to account for the pronounced difference in the physico-chemical properties observed.

Biomolecular interactions can be defined by combining thermodynamic data on the energetic properties of the interaction with high-resolution structural data. The development of high sensitivity isothermal titration calorimetric equipment provides a dramatic advance in the gathering of thermodynamic data, and the interactions between biological macromolecules can now be described with unprecedented accuracy.