Recent successes illustrate the role of mass spectrometry-based proteomics as an indispensable tool for molecular and cellular biology and for the emerging field of systems biology. These include the study of protein-protein interactions via affinity-based isolations on a small and proteome-wide scale, the mapping of numerous organelles, the concurrent description of the malaria parasite genome and proteome, and the generation of quantitative protein profiles from diverse species. The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.

Mass spectrometry-based proteomics

https://link.springer.com/content/pdf/10.1016/1044-0305(94)80016-2.pdf

An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.

FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death--inducing signaling complex.

A new method of desorption ionization is described and applied to the ionization of various compounds, including peptides and proteins present on metal, polymer, and mineral surfaces. Desorption electrospray ionization (DESI) is carried out by directing electrosprayed charged droplets and ions of solvent onto the surface to be analyzed. The impact of the charged particles on the surface produces gaseous ions of material originally present on the surface. The resulting mass spectra are similar to normal ESI mass spectra in that they show mainly singly or multiply charged molecular ions of the analytes. The DESI phenomenon was observed both in the case of conductive and insulator surfaces and for compounds ranging from nonpolar small molecules such as lycopene, the alkaloid coniceine, and small drugs, through polar compounds such as peptides and proteins. Changes in the solution that is sprayed can be used to selectively ionize particular compounds, including those in biological matrices. In vivo analysis is demonstrated.

https://science.sciencemag.org/content/sci/306/5695/471.full.pdf

Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization

Fascination with supramolecular chemistry over the last few decades has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nanoscopic dimensions Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries both inside and between the fields of chemistry, physics, and biology This chemistry is of continuing interest for synthetic chemists; partly because of the fascinating physical and chemical properties and the complex and varied aesthetically pleasing structures that supramolecules possess For scientists seeking to design novel molecular materials exhibiting unusual sensing, magnetic, optical, and catalytic properties, and for researchers investigating the structure and function of biomolecules, supramolecular chemistry provides limitless possibilities Thus, it transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field

In the early 1960s, the discovery of ‘crown ethers’, ‘cryptands’ and ‘spherands’ by Pedersen,1 Lehn,2 and Cram3 respectively, led to the realization that small, complementary molecules can be made to recognize each other through non-covalent interactions such as hydrogen-bonding, charge-charge, donor-acceptor, π-π, van der Waals, etc Such ‘programmed’ molecules can thus be self-assembled by utilizing these interactions in a definite algorithm to form large supramolecules that have different physicochemical properties than those of the precursor building blocks Typical systems are designed such that the self-assembly process is kinetically reversible; the individual building blocks gradually funnel towards an ensemble that represents the thermodynamic minimum of the system via numerous association and dissociation steps By tuning various reaction parameters, the reaction equilibrium can be shifted towards the desired product As such, self-assembly has a distinct advantage over traditional, stepwise synthetic approaches when accessing large molecules

It is well known that nature has the ability to assemble relatively simple molecular precursors into extremely complex biomolecules, which are vital for life processes Nature’s building blocks possess specific functionalities in configurations that allow them to interact with one another in a deliberate manner Protein folding, nucleic acid assembly and tertiary structure, phospholipid membranes, ribosomes, microtubules, etc are but a selective, representative example of self-assembly in nature that is of critical importance for living organisms Nature makes use of a variety of weak, non-covalent interactions such as hydrogen–bonding, charge–charge, donor–acceptor, π-π, van der Waals, hydrophilic and hydrophobic, etc interactions to achieve these highly complex and often symmetrical architectures In fact, the existence of life is heavily dependent on these phenomena The aforementioned structures provide inspiration for chemists seeking to exploit the ‘weak interactions’ described above to make scaffolds rivaling the complexity of natural systems

The breadth of supramolecular chemistry has progressively increased with the synthesis of numerous unique supramolecules each year Based on the interactions used in the assembly process, supramolecular chemistry can be broadly classified in to three main branches: i) those that utilize H-bonding motifs in the supramolecular architectures, ii) processes that primarily use other non-covalent interactions such as ion-ion, ion-dipole, π–π stacking, cation-π, van der Waals and hydrophobic interactions, and iii) those that employ strong and directional metal-ligand bonds for the assembly process However, as the scale and degree of complexity of desired molecules increases, the assembly of small molecular units into large, discrete supramolecules becomes an increasingly daunting task This has been due in large part to the inability to completely control the directionality of the weak forces employed in the first two classifications above Coordination-driven self-assembly, which defines the third approach, affords a greater control over the rational design of 2D and 3D architectures by capitalizing on the predictable nature of the metal-ligand coordination sphere and ligand lability to encode directionality Thus, this third strategy represents an alternative route to better execute the “bottom-up” synthetic strategy for designing molecules of desired dimensions, ranging from a few cubic angstroms to over a cubic nanometer For instance, a wide array of 2D systems: rhomboids, squares, rectangles, triangles, etc, and 3D systems: trigonal pyramids, trigonal prisms, cubes, cuboctahedra, double squares, adamantanoids, dodecahedra and a variety of other cages have been reported As in nature, inherent preferences for particular geometries and binding motifs are ‘encoded’ in certain molecules depending on the metals and functional groups present; these moieties help to control the way in which the building blocks assemble into well-defined, discrete supramolecules4

Since the early pioneering work by Lehn5 and Sauvage6 on the feasibility and usefulness of coordination-driven self-assembly in the formation of infinite helicates, grids, ladders, racks, knots, rings, catenanes, rotaxanes and related species,7 several groups - Stang,8 Raymond,9 Fujita,10 Mirkin,11 Cotton12 and others13,14 have independently developed and exploited novel coordination-based paradigms for the self-assembly of discrete metallacycles and metallacages with well-defined shapes and sizes In the last decade, the concepts and perspectives of coordination-driven self-assembly have been delineated and summarized in several insightful reviews covering various aspects of coordinationdriven self-assembly15 In the last decade, the use of this synthetic strategy has led to metallacages dubbed as “molecular flasks” by Fujita,16 and Raymond and Bergman,17 which due to their ability to encapsulate guest molecules, allowed for the observation of unique chemical phenomena and unusual reactions which cannot be achieved in the conventional gas, liquid or solid phases Furthermore, these assemblies found applications in supramolecular catalysis18,19 and as nanomaterials as developed by Hupp20 and others21,22

This review focuses on the journey of early coordination-driven self-assembly paradigms to more complex and discrete 2D and 3D supramolecular ensembles over the last decade We begin with a discussion of various approaches that have been developed by different groups to assemble finite supramolecular architectures The subsequent sections contain detailed discussions on the synthesis of discrete 2D and 3D systems, their functionalizations and applications

Supramolecular coordination: self-assembly of finite two- and three-dimensional ensembles.

Electrospray ionization has recently emerged as a powerful technique for producing intact ions in vacuo from large and complex species in solution. To an extent greater than has previously been possible with the more familiar "soft" ionization methods, this technique makes the power and elegance of mass spectrometric analysis applicable to the large and fragile polar molecules that play such vital roles in biological systems. The distinguishing features of electrospray spectra for large molecules are coherent sequences of peaks whose component ions are multiply charged, the ions of each peak differing by one charge from those of adjacent neighbors in the sequence. Spectra have been obtained for biopolymers including oligonucleotides and proteins, the latter having molecular weights up to 130,000, with as yet no evidence of an upper limit.

https://science.sciencemag.org/content/sci/246/4926/64.full.pdf

Electrospray ionization for mass spectrometry of large biomolecules

Chemistry has its origins as a quantitative science in the careful weighing of products and reactants by Lavoisier and his followers beginning some 200 years ago. Ever since then, the constantly evolving gravimetric balance has been a faithful servant of the laboratory chemist and has played a major role in developing the analytical methods that are the foundation of contemporary chemical science. Perhaps the ultimate stage in the evolution of that balance is represented by the modern mass spectrometer. It is able to determine with high precision the masses of individual atoms and molecules by transforming them into ions and measuring the response of their trajectories in vacuo to various combinations of electric and magnetic fields. Clearly, the sine qua non of such mass determination is the transformation of analyte atoms and molecules from their initial state in a sample to ions in vacuo ready for ”weighing.” Over the years, ingenious investigators have produced a variety of methods for achieving this transformation. One of them, electrospray ( E S ) ionization, has recently shown itself capable of producing intact ions, with multiple charges, from remarkably large, complex, and fragile parent species. Our assignment here is to review what has thus far been learned about this still uncommon technique and what it seems able to offer practitioners of mass spectrometric analysis. Our approach will be to set forth the present state of the ES ionization art in terms of a sort of menu of its procedures, processes, performance, and promise. Until very recently we have been almost the only group that has worked with ES ionization since the pioneering efforts of Malcolm Dole (1) some 20 years ago. Consequently, this review is more tutorial than most. Moreover, it may seem like a cook book that is overly preoccupied with the authors’ own culinary adventures. The reasoil is that many of the dishes to be described were first tried out in our own kitchen. Therefore, we earnestly urge the reader to remember what every gourmet knows: the piquancy of any dish on a bill of fare is due much less to its ingredients than to the skill of the chef whc. prepares it.

Shek Fu Wong

Papers

Electrospray ionization for mass spectrometry of large biomolecules

Electrospray ionization–principles and practice

Electrospray Ionization for Mass Spectrometry of Large Biomolecules