Solution-phase structure

Studies of amino acids and peptides have been a major component of VCD research. From a biophysical standpoint, VCD provides a unique source of solution phase structural and conformational information. In addition, the previously discussed molecules have been the focus of numerous theoretical investigations. The major role of electronic currents in generating biased VCD was first recognized in interpreting amino acid VCD spectra. The polypeptide spectra have provided a test for theoretical descriptions of VCD in a-helical polymers. 

Figure 21 Solution phase structure of 50. (Reprinted with permission from 93IC4677, Copyright 1993, American Chemical Society.)...

B. The Fluorine Probe Approach Solution-Phase Structure and... 

In order to correlate the solid state and solution phase structures, molecular modelling using the exciton matrix method was used to predict the CD spectrum of 1 from its crystal structure and was compared to the CD spectrum obtained in CHC13 solutions [23]. The matrix parameters for NDI were created using the Franck-Condon data derived from complete-active space self-consistent fields (CASSCF) calculations, combined with multi-configurational second-order perturbation theory (CASPT2). 

In this section, we present the results of computational studies of the five nucleic acid bases cytosine 13, guanine 14, adenine 15, thymine 16, and uracil 17. The canonical structures, those that are involved in the Watson-Crick base pairing within DNA, are drawn below. Other tautomers for each base can be energetically competitive with the canonical structure, and these other tautomers are invoked in some models of DNA mutations and anomalous DNA structures. The ensuing discussion focuses on the relative energies of the tautomers, in both the gas and solution phases. Structural changes that accompany this phase change are also noted. 

Benzylalkali metal compounds exist as aggregate structures in most solutions. NMR and UV-visible spectrophotometry are useful techniques for elucidating these solution-phase structures. Benzyllithium is dimeric in benzene solution the carbanion charge is probably more delocalized in THE solution. NMR studies of a THE solution of a-(dimethylamino)benzyllithium reveals a dynamic equilibrium between the and -structures (18) and (19). The monohapto isomer (18) is preferred thermodynamically.The effects of various donor ligands on this type of dynamic behavior in solution is continually being studied. ... 

When through-bond connectivity experiments are combined with the spatial information from buildup rates of NOESY cross peaks, proton-proton distances can be obtained by comparison with known bond lengths. The result can be a complete three-dimensional structure of biomolecules. Such solution-phase structures complement solid-phase information from X-ray crystallography. In this way, NMR spectroscopy has become a structural tool for obtaining detailed molecular geometries of complex molecules in solution. 

Lewis acidic hosts (Section V.A) illustrated important theoretical concepts such as the chelate effect and binding cooperativity, which have now been shown to exist for anion as well as cation binding. This work has also resulted in the crystallographic determination of eye-catching solid state receptor-anion complexes, while heteroelement NMR has allowed an accurate means of probing the solution phase structure of these complexes. Already, multinuclear tin systems are being built into functioning anion selective electrodes. 

JH NOESY and F NOESY spectra were used to determine the solution-phase structures of metallocenium homogeneous catalyst ion-pairs, e.g. [Cp2ZrMe]+[MeB(C5 5)3] and related systems.54 Cation-like intermediates formed by activation of zirconocenes, L2ZrCl2 (L = Cp, indenyl, fluorenyl) with methylaluminoxane, have been characterised using H NMR.55... 

The development of relatively softer ionization techniques of ESI and MALDI has engendered the use of mass spectrometry to determine conformations of proteins.122,12 -13° ESI has made especially tremendous strides, as it samples proteins directly from the native solvent environment. The belief is that the solution-phase structures of proteins are largely preserved during their conversion to the gas-phase ions with these methods thus, the spectrum obtained is a reflection of features of the protein s solution chemistry. 

In our own work there have been two main strands - the determination of solution-phase structures of heteronuclear clusters and the study of cluster reactions in which the metal framework is assembled or rearranges. In this work we have sought to obtain enhanced structural data as a result of the presence of more than one X-ray absorbing element (metal) in the cluster framework. Furthermore the presence of platinum or palladium in many of these systems leads to much structural variability. 

In an attempt to provide the first experimental insight into the solution-phase structure of 4, we, together with the groups of Ryzhkov and Hadad, recently reported a TRIR spectroscopic study [86]. We were unable to cleanly detect IR bands due to 4, but we did analyze the kinetics of bicyclo[2.1.0]pentane (5) formation despite the fact that certain IR bands for 5 in the C-H stretching region overlap with corresponding bands in biradical 4 (Scheme 2.7). This analysis was supported by computational investigations. 

Often the structures are maintained from solution to the solid state, and many of the H-bonded systems characterised to date are from solid-state structures obtained from X-ray crystallography (1,11,12]. It is more problematic to determine whether the solid state structure is maintained in solution, and a raft of less direct but nevertheless reliable methods can be utilised to define the solution-phase structures [12]. In the soUd state, there is often a wide variety of other reversible and weaker interactions (e.g. dipolar, van der Waals, jr - jr interactions) that supplement the main H-bonding forces that are the major factors in determining the structure [2,13-18]. 

With the development of relatively softer ionization techniques (ESI and MALDI), mass spectrometry has emerged as an option for the determination of conformational changes in proteins [2,16-23], It is believed that the solution-phase structure of a protein is largely preserved during ionization by these two methods. Therefore, the ESI and MALDI mass spectra of a protein reflect the features of its aqueous solution chemistry. The multiple-charging feature of ESI is also a valuable asset because it allows the study of much larger proteins. In this chapter a broad outline of the commonly used mass spectrometry-based techniques is presented. 

Overlapping resonances in 2D NMR have limited protein-structure elucidation to fairly small proteins. However, three- and four-dimensional methods have been developed that enable NMR spectroscopy to be further extended to larger and larger protein structures. A third dimension can be added, for example, to spread apart a H- H two-dimensional spectrum on the basis of the chemical shift of another nucleus, such as N or - C. In most three-dimensional experiments, the most effective methods for large molecules are used. Thus, COSY is not often employed, but experiments like NOESY-TOeSY and TOCSY-HMQC are quite effective. In some cases, the three dimensions all represent different nuclei such as H- C- N. These are considered variants of the HETCOR experiment. Multidimensional NMR is now capable of providing complete solution-phase structures to complement crystal structures from X-ray crystallography. Hence. NMR spectroscopy is now an important technique for determining structure.s and orientation.s of complex molecules in solution. 

Ah initio calculations of vibrational wavenumbers for lanthanide trihalides suggested some re-assignments of modes for ScBrs, YF3 and YCI3. Raman spectroscopy was used to characterise the solution-phase structures of [Ln WioOse] , where Ln = Y, La, Ce, Pr, Sm, Eu, Gd, Dy, Er or Lu, and [M WioOse], where M = Ce or Th. ... 

Salvadori and coworkers reported a solution phase structure of M3[Yb(binol)3] (YbMB) [132a]. The YbSB and YbPB catalysts were prepared from Yb(OTf)3 as metal source. Difference in solid phase structure and solution phase structure was studied in detail using UV-, CD-, and NMR-analysis. They also discussed the... 

Since the aqueous solution-phase structure of amino acids and peptides is normally zwitterionic, while that in the gas phase is frequently non-charge-sepa-rated, there is considerable interest in whether, and how completely, the complexes... 

There is, of course, controversy about whether a solution phase structure is retained in its entirety in the solvent-free environment of a mass spectrometer, " ") but for large macromolecular systems such as those referred to above, bound by many noncovalent interactions, there is evidence to suggest that macroscopic features of solution and even in vivo structures are retained. The growth and success of studies of macromolecular complexes by mass spectrometry increasingly places biological mass spectrometry as the first step in the structural analysis of unknown or as yet unquantified proteinrprotein architectures in short, it now has a role as a predictive tool. 

A full set of 40 Vhc and 40 Dhc has been measured by Hutin et al. for a three-layer stack aggregate of a linear porphyrin tetramer. The NMR and small-angle X-ray scattering data have allowed to elucidate the solution-phase structure of this well-defined aggregate. 

Proteins in solution are typically more mobile than those in a crystal. At equilibrium the protein in solution will fluctuate and its conformation is best represented as an ensemble of structures. This is not so bad The flexibility can leave certain portions of the protein unstructured. The mobile portions of the protein are often functionally important. Therefore, one can appreciate the disorder in the refined solution phase structure as a clue to the function of the protein and its equilibrium structure. When we seek to determine a protein s structure at room temperature we must appreciate that the native state consists of an ensemble of structures. 

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