Rapid Analysis of Trace Amounts of Amino Acid Derivatives by a Formyl Group-Installed Crystalline Sponge.

The Industries need techniques for the rapid structure analysis of amino acid derivatives. The amino acid derivatives are sometimes produced as impurities in the industrial production processes, and cause toxicity problems. Herein, we report the crystalline sponge (CS) method analysis of variety of amino acids using a formyl group installed CS crystal. Most amino acids possess a primary amino group, which can form Schiff-base with the formyl group under mild conditions. Thus, the formyl group installed CS crystal can efficiently capture the amino acids via Schiff-base formation. We successfully analyzed derivatives of 18 proteogenic amino acids, 6 non-proteogenic amino acids, and 4 dipeptides using the formyl group installed CS. We thus believe that the protocols shown in this study would serve the need of the industries.

Fluorescent and chromogenic organic probes to detect group 10 metal ions: design strategies and sensing applications.

Group 10 metals including Ni, Pd and Pt have been extensively applied in various essential aspects of human social life, material science, industrial manufactures, medicines and biology. The ionic forms of these metals are involved in several biologically important processes due to their strong binding capability towards different biomolecules. However, the mishandling or overuse of such metals has been linked to serious contamination of our ecological system, more specifically in soil and water bodies with acute consequences. Therefore, the detection of group 10 metal ions in biological as well as environmental samples is of huge significance from the human health point of view. Related to this, considerable efforts are underway to develop adequately efficient and facile methods to achieve their selective detection. Optical sensing of metal ions has gained increasing attention of researchers, particularly in the environmental and biological settings. Innovatively designed optical probes (fluorescent or colorimetric) are usually comprised of three basic components: an explicitly tailored receptor unit, a signalling unit and a clearly defined reporter unit. This review deals with the recent progress in the design and fabrication of fluorescent or colorimetric organic sensors for the detection of group 10 metal ions (Ni(II), Pd(II) and Pt(II)), with attention to the general aspects for design of such sensors.

Absolute Configuration Determination from Low ee Compounds by the Crystalline Sponge Method. Unusual Conglomerate Formation in a Pre-Determined Crystalline Lattice.

When chiral compounds with low enantiomeric excess (ee, R:S=m:n) were absorbed into the void of the crystalline sponge (CS), enantiomerically pure [(R)m (S)n ] chiral composites were formed, changing the centrosymmetric space group into non-centrosymmetric one. The absolute configuration of the analyte compounds was elucidated with a reasonable Flack (Parsons) parameter value. This phenomenon is characteristic to the "post-crystallization" in the pre-determined CS crystalline lattice, seldom found in common crystallization where the crystalline lattice is defined by an analyte itself. The results highlight the potential of the CS method for absolute configuration determination of low ee samples, an often encountered situation in asymmetric synthesis studies.

Strategy and Methodology in the Synthesis of Multicomponent Molecular Solids: The Quest for Higher Cocrystals.

Crystal engineering is the art and science of making crystals by design. Crystallization is inherently a purifying phenomenon. Bringing together more than one organic compound into the same crystal always needs deliberate action. Cocrystals are important because they offer a route to the controlled modulation of crystal properties. The route to cocrystal synthesis was opened up with the heterosynthon concept, which considers the complementary recognition of chemical groups from different molecules. Using this concept, binary cocrystals of enormous variety have been generated, even as crystal engineering has evolved into a form of solid-state supramolecular synthesis. Introducing a third component (a component is somewhat arbitrarily defined as an organic substance that is a solid at room temperature, mostly with the idea of excluding solvates) in a stoichiometric manner requires substantially greater effort and a careful balance of intermolecular interactions-their strengths, directional properties, and distance falloff characteristics. The first systematic ternary cocrystal synthesis was reported around 15 years ago. Drawing in a fourth component in stoichiometric amounts is exceedingly difficult, and we reported such syntheses in 2016. To date, a limited number of ternary cocrystals have been realized (around 120 in all, with a half from our group) and an even smaller number of quaternary cocrystals (around 30, all from our group, barring one). It is impressive that our experiments largely yielded the intended higher cocrystal (three- or four-component) with very small traces of contaminating binaries and pure compounds. A fifth or sixth component may be brought into the solid in the manner of a solid solution in that these components are situated at one of the sites of the quaternary cocrystal. To date, five components have not been included stoichiometrically within the same crystal. This is still an open challenge. The merit in synthesizing (higher) cocrystals is that one can systematically engineer property modularity: Each component is associated with a distinct property. This is important in the pharmaceutical industry, where each component can, in principle, confer a different, desirable property-drug action, solubility, or permeability. However, difficult synthetic targets are also addressed in chemistry simply because they are there. The intellectual satisfaction in making something that is very difficult to make renders the enterprise worthwhile in itself, and new chemistry usually gets uncovered in the process. The development of synthetic organic chemistry can undoubtedly be credited to various reliable methods for chemical transformations, and many difficult total syntheses were achieved by employing these methods over two centuries of research. In contrast, supramolecular synthesis (of multicomponent cocrystals and other assemblies) is in no way at a similar level of sophistication because the subject is still relatively young. Our group and others have reported the synthesis of many higher cocrystals with reliable, reproducible, and robust design strategies. There is a general perception that the isolation of some of these cocrystals is a matter of luck! The crux of this Account is that far from being a serendipitous matter, higher cocrystals may only be made with a judicious combination of strategy and methodology-the essence of synthesis.

Chiral Crystalline Sponges for the Absolute Structure Determination of Chiral Guests.

Chiral crystalline sponges with preinstalled chiral references were synthesized. On the basis of the known configurations of the chiral references, the absolute structures of guest compounds absorbed in the pores of the crystalline sponges can be reliably determined without crystallization or chemical modification.

X-ray Structure Analysis of Ozonides by the Crystalline Sponge Method.

The crystalline sponge method was used for the X-ray structure analysis of ozonide compounds. As this new technique requires only microgram quantities of the samples, structural analysis can be conducted without product isolation, isomer separation, or crystallization and most importantly without any risk of explosion.

Four- and five-component molecular solids: crystal engineering strategies based on structural inequivalence.

A synthetic strategy is described for the co-crystallization of four- and five-component molecular crystals, based on the fact that if any particular chemical constituent of a lower cocrystal is found in two different structural environments, these differences may be exploited to increase the number of components in the solid. 2-Methylresorcinol and tetramethylpyrazine are basic template molecules that allow for further supramolecular homologation. Ten stoichiometric quaternary cocrystals and one quintinary cocrystal with some solid solution character are reported. Cocrystals that do not lend themselves to such homologation are termed synthetic dead ends.

Quaternary cocrystals: combinatorial synthetic strategies based on long-range synthon Aufbau modules (LSAM).

A synthetic strategy is outlined whereby a binary cocrystal may be developed in turn into a ternary and finally into a quaternary cocrystal. The strategy hinges on the concept of the long-range synthon Aufbau module (LSAM) which is a large supramolecular synthon containing more than one type of intermolecular interaction. Modulation of these interactions may be possible with the use of additional molecular components so that higher level cocrystals are produced. We report six quaternary cocrystals here. All are obtained as nearly exclusive crystallization products when four appropriate solid compounds are taken together in solution for crystallization.

Combinatorial selection of molecular conformations and supramolecular synthons in quercetin cocrystal landscapes: a route to ternary solids.

The crystallization of 28 binary and ternary cocrystals of quercetin with dibasic coformers is analyzed in terms of a combinatorial selection from a solution of preferred molecular conformations and supramolecular synthons. The crystal structures are characterized by distinctive O-H⋯N and O-H⋯O based synthons and are classified as nonporous, porous and helical. Variability in molecular conformation and synthon structure led to an increase in the energetic and structural space around the crystallization event. This space is the crystal structure landscape of the compound and is explored by fine-tuning the experimental conditions of crystallization. In the landscape context, we develop a strategy for the isolation of ternary cocrystals with the use of auxiliary template molecules to reduce the molecular and supramolecular 'confusion' that is inherent in a molecule like quercetin. The absence of concomitant polymorphism in this study highlights the selectivity in conformation and synthon choice from the virtual combinatorial library in solution.

Intermolecular atom-atom bonds in crystals - a chemical perspective.

Short atom-atom distances between molecules are almost always indicative of specific intermolecular bonding. These distances may be used to assess the significance of all hydrogen bonds, including the C-H⋯O and even weaker C-H⋯F varieties.

Crystal structure and prediction.

The notion of structure is central to the subject of chemistry. This review traces the development of the idea of crystal structure since the time when a crystal structure could be determined from a three-dimensional diffraction pattern and assesses the feasibility of computationally predicting an unknown crystal structure of a given molecule. Crystal structure prediction is of considerable fundamental and applied importance, and its successful execution is by no means a solved problem. The ease of crystal structure determination today has resulted in the availability of large numbers of crystal structures of higher-energy polymorphs and pseudopolymorphs. These structural libraries lead to the concept of a crystal structure landscape. A crystal structure of a compound may accordingly be taken as a data point in such a landscape.

Combinatorial crystal synthesis: structural landscape of phloroglucinol:1,2-bis(4-pyridyl)ethylene and phloroglucinol:phenazine.

A large number of crystal forms, polymorphs and pseudopolymorphs, have been isolated in the phloroglucinol-dipyridylethylene (PGL:DPE) and phloroglucinol-phenazine (PGL:PHE) systems. An understanding of the intermolecular interactions and synthon preferences in these binary systems enables one to design a ternary molecular solid that consists of PGL, PHE, and DPE, and also others where DPE is replaced by other heterocycles. Clean isolation of these ternary cocrystals demonstrates synthon amplification during crystallization. These results point to the lesser likelihood of polymorphism in multicomponent crystals compared to single-component crystals. The appearance of several crystal forms during crystallization of a multicomponent system can be viewed as combinatorial crystal synthesis with synthon selection from a solution library. The resulting polymorphs and pseudopolymorphs that are obtained constitute a crystal structure landscape.

Crystal landscape in the orcinol:4,4'-bipyridine system: synthon modularity, polymorphism and transferability of multipole charge density parameters.

Polymorphism in the orcinol:4,4'-bipyridine cocrystal system is analyzed in terms of a robust convergent modular phenol⋯pyridine supramolecular synthon. Employing the Synthon Based Fragments Approach (SBFA) to transfer the multipole charge density parameters, it is demonstrated that the crystal landscape can be quantified in terms of intermolecular interaction energies in the five crystal forms so far isolated in this complex system. There are five crystal forms. The first has an open, divergent O-H⋯N based structure with alternating orcinol and bipyridine molecules. The other four polymorphs have different three-dimensional packing but all of them are similar at an interaction level, and are based on a modular O-H⋯N mediated supramolecular synthon that consists of two orcinol and two bipyridine molecules in a closed, convergent structure. The SBFA method, which depends on the modularity of synthons, provides good agreement between experiment and theory because it takes into account the supramolecular contribution to charge density. The existence of five crystal forms in this system shows that polymorphism in cocrystals need not be considered to be an unusual phenomenon. Studies of the crystal landscape could lead to an understanding of the kinetic pathways that control the crystallization processes, in other words the valleys in the landscape. These pathways are traditionally not considered in exercises pertaining to computational crystal structure prediction, which rather monitors the thermodynamics of the various stable forms in the system, in other words the peaks in the landscape.

Structural landscape of the 1 : 1 benzoic acid : isonicotinamide cocrystal.

The acid-pyridine heterosynthon may be used as a "molecular" module to probe the structural landscape of the benzoic acid : isonicotinamide 1 : 1 cocrystal, BA : INA. Experimental structures of 1 : 1 cocrystals of fluorobenzoic acids (FBA) with isonicotinamide (INA) contain this heterosynthon and correspond to high-energy structures of 1 : 1 BA : INA.

Structural landscape of benzoic acid: using experimental crystal structures of fluorobenzoic acids as a probe.

Experimental crystal structures of mono and polyfluorinated benzoic acids correspond to high energy computed crystal structures of benzoic acid itself, thereby permitting access to its structural landscape.

Extending the supramolecular synthon based fragment approach (SBFA) for transferability of multipole charge density parameters to monofluorobenzoic acids and their cocrystals with isonicotinamide: importance of C-H···O, C-H···F, and F···F intermolecular regions.

An extension of the supramolecular synthon-based fragment approach (SBFA) method for transferability of multipole charge density parameters to include weak supramolecular synthons is proposed. In particular, the SBFA method is applied to C-H···O, C-H···F, and F···F containing synthons. A high resolution charge density study has been performed on 4-fluorobenzoic acid to build a synthon library for C-H···F infinite chain interactions. Libraries for C-H···O and F···F synthons were taken from earlier work. The SBFA methodology was applied successfully to 2- and 3-fluorobenzoic acids, data sets for which were collected in a routine manner at 100 K, and the modularity of the synthons was demonstrated. Cocrystals of isonicotinamide with all three fluorobenzoic acids were also studied with the SBFA method. The topological analysis of inter- and intramolecular interaction regions was performed using Bader's AIM approach. This study shows that the SBFA method is generally applicable to generate charge density maps using information from multiple intermolecular regions.

A study of thermal denaturation/renaturation in DNA using laser light scattering: a new approach.

The thermal denaturation/renaturation processes in E. coli and eukaryotic DNAs have been studied using the laser light scattering (LS) technique. The differential scattering intensity curve has been utilized to determine the transition temperature T(m). The effect of solution pH on DNA thermal denaturation has been examined. It has been shown clearly that LS is an extremely sensitive method (more than the UV absorption method) and reveals even the subtler effects such as the pre-transition fluctuations, and that the DNA denaturation is prominently affected by pH. The dependence of melting temperature (T(m)) on composition of DNA, number of base pairs and base sequences has also been investigated. It has been observed that depending upon its base sequence, the T(m) decreases in the case of renatured DNAs. The results have been compared with the UV absorption studies.