Non covalent interactions are valuable tools for crystal engineering. Hydrogen bonding often plays a central role for molecular association among possible non covalent interactions. Together with hydrogen bonding, arene-arene interactions and van der Waals interactions can control crystal assembly. Understanding non covalent interactions permits the design of molecules whose functionalities can interact non covalently so that molecules will pack in a predicted fashion. For two decades Prof. Mash's group has been studying crystal packing based on a piperazinedione core scaffold which can have three orthogonal non covalent interactions and lead to controlled three dimensional crystal packing. Alkoxy-substituted piperazinediones were previously studied for crystal packing and liquid crystal properties. It was found that alkoxy piperazinediones pack in three dimesions as designed and exhibit interesting thermochemical properties. Given that small changes in structure can cause large changes in packing and liquid crystal properties, the replacement of alkoxy groups with alkyl groups in molecules provides an opportunity to investigate the role of oxygen in crystal packing and liquid crystal properties. A series of alkyl piperazinediones was synthesized in a convergent way where an intermediate tetrabromide was converted into a series of tetra alkyne piperazinediones, then into tetra alkyl piperazinediones. This approach overcame limitations in the synthesis of alkoxy piperazinediones, where every target molecule requires 10 to 11 steps starting from 2,3-dimethylbenzene-1,4-diol (Scheme 2.1). Crystal structure analyses were done for three different piperazinediones. It appears that crystal packing of alkyl piperazinediones mimics that of alkoxy piperazinediones.

Thesis submitted in fulfilment of the requirements for the degree Master of Technology: Chemistry in the Faculty of Applied Science at the CAPE PENINSULA UNIVERSITY OF TECHNOLOGY 2014 / Crystal engineering based upon acid: base compounds have been studied in this thesis. Selected phenolic acids such as: vanillic acid (VA), phenylacetic acid (PAA), 4-hydroxyphenylacetic acid (HPAA), 3-chloro-4-hydroxyphenylacetic acid (CHPAA), caffeic acid (CFA), p-coumaric acid (pCA), trans-ferulic acid (tFER), 2-phenylpropionic acid (PPA) and 2-phenylbutyric acid (PBA) were the main compounds investigated. These phenolic acids have formed co-crystals/co-crystal hydrates, salts/salt hydrates and hybrid salt-co-crystals with acridine (ACRI), caffeine (CAF), cinchonidine (CIND), isonicotinamide (INM), isonicotinic acid (INA), nicotinamide (NAM), quinidine (QUID), quinine (QUIN), theobromine (THBR), theophylline (THPH) and urea (U). The two racemic compounds 2-phenylpropionic acid (PPA) and 2-phenylbutyric acid (PBA) were used to study chiral discrimination leading to the understanding of separation enantiomers. Compounds were prepared in different solvents (alcohols, ketone and distilled water) to investigate the relationship between solvents used and the crystalline product obtained. (If there is any effect on the crystalline compound obtained by changing the solvent). The structures were elucidated using single crystal X-ray diffraction. Ground products of obtained compounds were characterized by powder X-ray diffraction (PXRD). Thermal analyses like thermogravimetry (TG), differential scanning calorimetry (DSC) and hot stage microscopy (HSM) were used for the determination of thermal character of the new compounds. IR was also performed to characterize the new compounds. Non-isothermal TG was utilised to obtain kinetic parameters for the water and the methanol release in (pCA−)(QUIN+)•pCA•MeOH•H2O. A selective experiment was done in which quinidine and quinine were used to compete between selected phenolic acids (PAA and HPAA). viii The comparison of the crystal structures determined showed that, changing the phenolic acid while using the same co-crystal former has a significant effect on the type of compounds obtained. The obtained crystal structures were either co-crystal/co-crystal hydrates, salts/salt hydrates or hybrid salt-co-crystals which formed network via means of supramolecular interactions.

Organic semiconductors are of interest because low processing temperatures and cost which make such materials candidates for flexible electronics. The charge transport properties of the material are largely dependent on solid-state arrangement of the molecules. This thesis focuses on co-crystallization as a means to achieve [2+2] photodimerization with organic semiconductors, the impact the co-crystal former has on mobility, the use of a co-crystal former to obtain different conformations of a flexible system, and the ability to detect the change in conformation by infrared spectroscopy. [2+2] photodimerization is studied as a way to alter the orientation of the π-systems in the solid state. To align a semiconductor building block into an orientation suitable for [2+2] photodimerization a co-crystallization method was used. The result of the photoreaction is the formation of a dimer in which the π-systems of the semiconductor building block are in a different orientation then before. Changes in the physical properties of the material through photodimerization are explored as a method for patterning thin films. The impact the second component has on the overall mobility in our system is examined. The second component is not expected to act as a semiconductor and the impact on mobility the by its inclusion in the solid is unknown. The impact of a second component on mobility is studied by observing the mobility of multiple co-crystals along with the mobility of the single component. It was found that the mobility could be increased by a factor of approximately 200 with addition of a second component. The mobility change seen in the two-component crystals is equated to the changes observed in the crystal packing. The conformation a molecule adopts in a solid can vary. It was discovered that the addition of a second component can be used to select the major conformation a bithiophene adopts in a solid. The change in conformation changes the orientation of the π-systems between molecules within the solid. The ability for a second component to alter the conformation of a bithiophene is explored. Infrared spectroscopy is used as a facial method to detect the change in the bithiophene conformation.

Transition metal clusters are a unique class of chemical substances. Not only do they have well-defined molecular structures, they also exhibit interesting and potentially useful properties that are inherent to metal-metal bonded species. They may be viewed as atom-like building blocks with adjustable properties. Detailed in this dissertation are the efforts to develop synthetic methodologies necessary to bring a cluster system out of the limited sphere of fundamental cluster chemistry and into general synthetic applicability. Specifically, the design and synthesis, structural characterization, and synthetic applications of the cluster complexes of the [Re₆(μ₃-Se)₈]²⁺ core will be discussed. Chapter 1 provides necessary background information of the [Re₆(μ₃-Se)₈]²⁺ core-containing cluster system, the rationales of cluster-supported synthetic and structural chemistry, and the impetus for these endeavors. Chapter 2 details the synthetic applications of stereospecific complexes of the [Re₆(μ₃-Se)₈]²⁺ clusters for the assembly of nanoscopic multicluster arrays using molecular and supramolecular approaches. The synthesis and structural characterization of a triangle-shaped tricluster array and a tetracluster assembly composed of two hydrogen-bonded diclusters are described. Chapters 3 and 4 describe the synthesis of the [Re₆(μ₃-Se)₈]²⁺ core-containing cluster complexes with the water-soluble 1,3,5-triaza-7-phosphaadamantane (PTA) ligand and the chemistry of these cluster-complex ligands for the coordination of a variety of secondary metal ions. In Chapter 5, the supramolecular chemistry of the cluster-PTA complexes with Ag(I) is detailed. The coordination of Ag(I) to a cluster complex with two PTA ligands disposed trans- to each other produces a 2-dimensional, porous solid with nano-sized hydrophobic pores that are potentially useful for storage of hydrocarbons and for occlusion of certain substrates for activation and possible catalysis. Chapter 6 summarizes the efforts to synthesize cluster-polymer hybrid materials by using an initiating cluster complex for the controlled radical polymerization. The synthesis, spectroscopic and structural characterizations of a novel cluster complex with an initiating ligand are described. Preliminary results of its application for the controlled polymerization of methyl methacrylate are detailed. Chapter 7 draws a set of conclusions based on the results presented in Chapters 2-6 and elaborates on some future directions aimed at moving one step forward the cluster-supported synthetic and materials chemistry.

No description available.

Yes / The properties of nitrogen centres acting either as hydrogen-bond or Brønsted acceptors in solid molecular acid–base complexes have been probed by N 1s X-ray photoelectron spectroscopy (XPS) as well as 15N solid-state nuclear magnetic resonance (ssNMR) spectroscopy and are interpreted with reference to local crystallographic structure information provided by X-ray diffraction (XRD). We have previously shown that the strong chemical shift of the N 1s binding energy associated with the protonation of nitrogen centres unequivocally distinguishes protonated (salt) from hydrogen-bonded (co-crystal) nitrogen species. This result is further supported by significant ssNMR shifts to low frequency, which occur with proton transfer from the acid to the base component. Generally, only minor chemical shifts occur upon co-crystal formation, unless a strong hydrogen bond is formed. CASTEP density functional theory (DFT) calculations of 15N ssNMR isotropic chemical shifts correlate well with the experimental data, confirming that computational predictions of H-bond strengths and associated ssNMR chemical shifts allow the identification of salt and co-crystal structures (NMR crystallography). The excellent agreement between the conclusions drawn by XPS and the combined CASTEP/ssNMR investigations opens up a reliable avenue for local structure characterization in molecular systems even in the absence of crystal structure information, for example for non-crystalline or amorphous matter. The range of 17 different systems investigated in this study demonstrates the generic nature of this approach, which will be applicable to many other molecular materials in organic, physical, and materials chemistry. / EPSRC, Sanofi-Aventis

Yes / The creation of ternary multi-component crystals through the introduction of 18-crown-6 to direct the hydrogen-bonding motifs of the other molecular components was investigated for 3,5-dinitrobenzoic acid (3,5-dnba) with 4-aminobenzoic acid (4-aba). The creation of a binary complex between 18-crown-6 and 4-aba (C12H24O6·2C7H7NO2)2 and a ternary salt between 3,5-dnba, 18-crown-6 and 4-aba (C12H24O6·C7H8NO2+·C7H3N2O6−·C7H4N2O6) were confirmed by single-crystal structure determination. In both structures, the amino molecules bind to the crown ether through N—H...O hydrogen bonds, leaving available only a single O atom site on the crown with restricted geometry to potentially accept a hydrogen bond from 3,5-dnba. While 3,5-dnba and 4-aba form a binary co-crystal containing neutral molecules, the shape-selective nature of 18-crown-6 preferentially binds protonated amino molecules, thereby leading to the formation of the ternary salt, despite the predicted low concentration of the protonated species in the crystallizing solution. Thus, through the choice of crown ether it may be possible to control both location and nature of the available bonding sites for the designed creation of ternary crystals.

Yes / The non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and tolfenamic acid (TFA) have a close resemblance in their molecular scaffold, whereby a methyl group in MFA is substituted by a chloro group in TFA. The present study demonstrates the isomorphous nature of these compounds in a series of their multicomponent solids. Furthermore, the unique nature of MFA and TFA has been demonstrated while excavating their alternate solid forms in that, by varying the drug (MFA or TFA) to coformer [4-dimethylaminopyridine (DMAP)] stoichiometric ratio, both drugs have produced three different types of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate (1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close similarity of TFA and MFA structures, these multicomponent solids have shown an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their similarity in terms of space group and structural packing with isomorphic nature among the pairs. Herein, the experimental results are generalized in a broader perspective for predictably identifying any possible new forms of comparable compounds by mapping their crystal structure landscapes. The utility of such an approach is evident from the identification of polymorph VI of TFA from hetero-seeding with isomorphous MFA form I from acetone–methanol (1:1) solution. That aside, a pseudopolymorph of TFA with dimethylformamide (DMF) was obtained, which also has some structural similarity to that of the solvate MFA:DMF. These new isostructural pairs are discussed in the context of solid form screening using structural landscape similarity / Department of Science and Technology (DST/SJF/CSA-02/2014–15); Royal Pharmaceutical Society of Great Britain for seed corn funding (2018–19); INSPIRE fellowship from Department of Science and Technology, Government of India; IISER-Kolkata (instrumental facilities and fellowships)

Thesis (PhD (Chemistry and Polymer Science))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: The primary objective of the work was to prepare and investigate new porous materials using the principles of crystal engineering. Both organic and metal-organic systems were studied and the work can best be divided into two separate sections: 1. The crystal engineering of Dianin’s Compound, a well-known organic host. 2. The design and synthesis of a series of related porous coordination compounds consisting of discrete, dinuclear metallocycles. The first section discusses the synthetic modification of Dianin’s compound in order to engineer a new clathrate host with an altered aperture size. Although this study ultimately failed to isolate the host material in its porous guest-free form, the work led to the discovery of a chiral host framework that aligns guest molecules in a polar fashion, and consequently displays non-linear optical properties. These findings are unprecedented in the long history of crystal engineering of Dianin’s compound and its analogues. This section also describes desorption studies of the new inclusion compound, as well as the known thiol analogue of Dianin’s compound. Systematic characterisation of these desorbed phases has raised interesting fundamental questions about desolvation processes in general. The second section constitutes the major portion of the work. A series of related isostructural coordination metallocycles were synthesised and their structure-property relationships were investigated using a variety of complementary techniques. These metallocyclic compounds all crystallise as solvates in their as-synthesised forms, and different results are obtained upon desolvation of the materials. In each case, desolvation occurs as a single-crystal to single-crystal transformation and three new “seemingly nonporous” porous materials were obtained. A single-crystal diffraction study under various pressures of acetylene and carbon dioxide was conducted for one of the porous metallocycles. This enabled the systematic study of the host deformation with increasing equilibrium pressure (i.e. with increasing guest occupancy). The observed differences in the sorption behaviour for acetylene and carbon dioxide are discussed and rationalised. Gravimetric gas sorption isotherms were also recorded for the three different porous materials and the diffusion of bulkier molecules through the host was also investigated structurally. Finally, a possible gas transport mechanism is postulated for this type of porous material (i.e. seemingly nonporous), and this is supported by thermodynamic and kinetic studies, as well as molecular mechanics and statistical mechanics simulations. / AFRIKAANSE OPSOMMING: Die primêre doel van die werk was om nuwe poreuse materiale te berei en deur die toepassing van beginsels van kristalmanipulasie (E. crystal engineering) te ondersoek. Beide organiese- en metaal-organiese sisteme is bestudeer en die werk kan in twee kategorieë verdeel word: 1. Die kristalmanipulasie van Dianin se verbinding, ’n bekende organiese gasheer. 2. Die ontwerp en sintese van ’n reeks verwante poreuse koördinasieverbindings wat uit diskrete, binukleêre metallosiklieseverbindings bestaan. Die eerste deel handel oor die sintetiese verandering van Dianin se verbinding om ’n nuwe klatraatgasheer met ’n veranderde spleetgrootte te vorm. Alhoewel hierdie studie nie daarin geslaag het om die gasheer in sy poreuse “gas(E. guest)-vrye” vorm te isoleer nie, het die werk ’n nuwe chirale gasheerraamwerk aan die lig gebring. Die chirale gasheerraamwerk rig gas(E. guest)molekules in eendimensionele kolomme op ’n polêre wyse en gevolglik vertoon die materiaal nie-linieêre optiese eienskappe. Hierdie resultaat is ongekend in die lang geskiedenis van kristalmanipulasie van Dianin se verbindings en sy analoë. Hierdie afdeling beskryf ook die desorpsiestudies van die nuwe gasheer, en die tiol-afgeleide van Dianin se verbinding. Die sistematiese karakterisering van hierdie fases na desorpsie het fundamentale vrae na vore gebring oor desorpsieprosesse oor die algmeen. Die tweede afdeling maak die grootste gedeelte van die werk uit. ’n Reeks verwante isostrukturele ringvormige koördinasieverbindings is gesintetiseer en hul struktuureienskap verhoudings is deur ’n verskeidenheid komplementêre tegnieke ondersoek. Hierdie metallosiklieseverbindings kristalliseer almal in gesolveerde toestand vanaf sintese en verskillende resultate word verkry wanneer die verbinding desorpsie ondergaan. In alle gevalle vind gas(E. guest)desorpsie as enkel-kristal na enkel-kristal omsettings plaas en drie nuwe ‘oënskynlik nie-poreuse’ poreuse materiale is bekom. ’n Enkelkristal diffraksiestudie onder verskeie gasdrukke is met asetileen en koolstofdioksied uitgevoer vir een van die poreuse metallosiklieseverbindings. Dit het die geleentheid geskep om die mate waartoe die gasheer as gevolg van verhoogde ewewigsdruk vervorm (en dus toename in gasheerbesetting), sistematies te bestudeer. Die waargenome verskille in sorpsie-optrede vir asetileen en koolstofdioksied word bespreek en verklaar. Gravimetriese gassorpsie isoterme is ook vir die drie poreuse materiale verkry en die diffusie van groter molekules deur die gasheer is struktureel ondersoek. Laastens word ’n moontlike gasoordragmeganisme vir hierdie tipe poreuse (i.e. oënskynlik nie-poreuse) materiale gepostuleer. Hierdie bespreking word deur termodinamiese en kinetiese studies aangevul, sowel as molekulêre-meganika en statisties-meganiese studies.

Non-covalent interactions are of great importance in biology, chemistry, and material sciences. Although much information about different types of non-covalent interactions is available, incorporating them in a molecular design to generate a molecule that can undergo association to form a molecular assembly with bulk properties of interest is a challenge. To understand and harness intermolecular interactions, we have designed an indane 2,5-diketopiperazine (DKP) scaffold. Crystal engineering studies with this scaffold show that the molecules assemble into one dimensional tapes via reciprocal amide hydrogen bonds, tapes assemble into two dimensional sheets via arene-arene interactions, and sheets assemble into three dimensional solids via van der Waals contacts. A series of tetraalkoxy-substituted DKPs previously investigated exhibited liquid crystalline behavior. A new class of DKPs with one alkoxy substituent, rather than two, on each benzene ring has been synthesized. Thermochemical studies of the new DKPs by differential scanning calorimetry and polarized optical microscopy show that they are not liquid crystalline as expected. However, in the process of making the DKPs, conformationally constrained tyrosine analogues, (R)- and (S)-5-hydroxy-2-aminoindan- 2-carboxylic acids, were prepared by chromatographic separation of diastereomeric dipeptide derivatives formed from N-Boc-L-phenylalanine. Absolute configurations were assigned by X-ray crystallographic analysis. The series of tetraalkoxy-substituted DKPs showed a remarkable trend in freezing point. The freezing point for the series decreases with an increase in alkyl chain length. To understand the relationship between the crystal packing interactions and the freezing point trend, a study of the association of DKPs in solution by NMR was initiated. An Nmethylated 2,5-diketopiperazine was previously synthesized and studied by NMR using chloroform as solvent to obtain equilibrium constants for self association. Attempted multi-step syntheses of a more lipophilic N-3,7-dimethyloctyl 2,5-diketopiperazine, which was expected to have solubility in non-interfering solvents such as carbon disulfide, benzene, and carbon tetrachloride, failed. In response, a direct and concise method for accessing N-alkyl DKPs was developed, and an N-decyl 2,5-diketopiperazine was synthesized. X-ray crystallographic analysis of the N-decyl 2,5-diketopiperazine reveals formation of dimers via hydrogen bonding in the solid state.