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Die Aufgabe des synthetischen Chemikers besteht darin neue Moleküle, Bauelemente oder Medikamente aus einfachen Edukten herzustellen. Die wachsende Komplexität dieser synthetischen Produkte bedingt jedoch, dass die Entwicklung der dazu benötigten Werkzeuge ebenso schritthalten muss. Licht ist mit seiner herausragenden räumlichen, zeitlichen und energetischen Auflösung sowie seinem nicht-invasiven Charakter den traditionell verwendeten Stimuli überlegen. In dieser Arbeit wurde durch die Kombination eines molekularen Photoschalters mit der Diels-Alder-Reaktion die Photokontrolle über eine dynamisch-kovalente Reaktion erlangt. Das Ergebnis der Reaktion eines furyl-substituierten Diarylethens mit Maleinimid konnte ausschließlich durch die Bestrahlung mit Licht unterschiedlicher Farbe bestimmt werden. Dieses prototypische System wurde dann unter Erhalt seiner photochemischen Eigenschaften für die Anwendung unter physiologischen Bedingungen weiterentwickelt. Es konnte die photoreversible Freisetzung therapeutisch wirksamer Konzentrationen verschiedener Anti-Tumor-Medikamente in gepufferter, wässriger Lösung bei Körpertemperatur durch bioorthogonales sichtbares Licht ausgelöst werden. Weiterhin wurden die Feinabstimmung der Freisetzung dieser photoschaltbaren Diels-Alder-Addukte und eine ausführliche Untersuchung der Freisetzungs-Dynamiken gezeigt. Hierdurch wurde das System auf eine Stufe gehoben, an der in vivo Anwendungen erwägt werden können. Des Weiteren wurden die Grundlagen zur Implementierung der photokontrollierbaren Diels-Alder-Reaktion in der reversiblen kovalenten Funktionalisierung von Kohlenstoffnanoröhren gelegt. Trotzdem noch keine erfolgreiche Funktionalisierung nachgewiesen werden konnte, wurde durch die Untersuchung der zugrundeliegenden Prinzipien der Weg für die Anwendung fortgeschrittener Techniken zur Modulation physikochemischer Eigenschaften von sp2-Kohlenstoff Allotropen geebnet. / The synthetic chemist’s profession is devoted to the formation of chemical bonds to create new molecules, building blocks, or drugs from basic starting materials. However, the growing complexity of these synthetic products necessitates that the development of the tools to fulfill this task must also keep pace. Light as a stimulus with its superior spatial, temporal, as well as energetic resolution in combination with its non-invasive character outperforms the traditional means to control a chemical reaction, such as heat, pressure, or pH, clearly. In this work, the unprecedented reversible photocontrol over a dynamic covalent reaction was established by the combination of a molecular photoswitch and the well-known Diels-Alder reaction. The outcome of the reaction of a furyl-substituted diarylethene and maleimide could be determined exclusively by illumination with differently colored light. This prototypical system was then advanced for the application under physiological conditions while retaining its superior photochemical properties. The release of therapeutically effective concentrations of different antitumor agents could be photoreversibly triggered in buffered, aqueous solution at body temperature employing bioorthogonal visible light. It is shown how the release properties of these photoswitchable prodrugs can be fine-tuned and a thorough investigation of the release dynamics is presented promoting this system to a level where in vivo application can be considered. Furthermore, the foundations for the implementation of the photocontrollable Diels-Alder reaction in the reversible covalent functionalization of carbon nanotubes have been laid. Despite the fact that a successful functionalization has not yet been achieved, the basic principles were investigated and have paved the way for the application of more advanced techniques to effectively modulate the physicochemical properties of sp2-carbon allotropes.

Le contrôle de la viscosité des lubrifiants moteur est un enjeu clé dans la réduction de la consommation en carburant des moteurs thermiques. Une nouvelle approche basée sur l’utilisation de polymères thermo-associatifs a été développée pour diminuer la perte de viscosité naturelle des lubrifiants avec la température. Pour ce faire, des polymères complémentaires de faibles masses molaires (pour l’application moteur visée) qui peuvent s’associer réversiblement via la réaction d’échange diol-ester boronique lorsque la température augmente ont été conçus et synthétisés. Les faibles masses molaires des polymères et le caractère dynamique de la liaison ester boronique permettent de diminuer la sensibilité de ces systèmes aux forts cisaillements présents dans le moteur, en limitant notamment la rhéofluidification de ces lubrifiants. L’association des polymères est provoquée par l’augmentation d’accessibilité des fonctions portées par les polymères avec la température. L’association réversible des polymères thermo-associatifs a été mise en évidence dans les huiles apolaires par l’augmentation de la viscosité relative des solutions avec la température sur plusieurs cycles de chauffage-refroidissement. Une partie de l’étude a été consacrée à l’amélioration de la stabilité thermique des polymères dans le but de maintenir les bonnes propriétés lubrifiantes des formulations jusqu’à 150°C. Un grand nombre de polymères de natures, de tailles et d’architectures différentes ont été synthétisés. L’étude rhéologique en écoulement de ces polymères seuls et en formulations thermo-associatives a permis de mettre en évidence l’importance de ces différents leviers pour faire varier et contrôler les propriétés des solutions en fonction de la température. / Controlling the viscosity of engine lubricants is a key issue to reduce the fuel consumption of engines. A new approach based on the use of thermo-associative polymers has been developed in order to compensate the natural loss of viscosity of lubricants when the temperature increases. To this aim, complementary low molecular weight polymers (for engine targeted application) that can reversibly associate with temperature through the diol-boronic ester exchange reaction have been designed and synthesized. The low molecular weights of the polymers and the dynamic behavior of the boronic ester bond decrease the high shear sensitivity of the system and so limits the shear-thinning behavior of the lubricant. The increase of polymeric function availability as the temperature rises induces polymer association. The reversibility of the thermo-associative association of polymers in non polar oil is seen over several cycles of warming-cooling with the increase of the relative viscosity of the solutions with increasing temperature. Part of the study was also dedicated to the improvement of polymers’ thermal stability in order to maintain the good lubricant properties of the thermo-associative formulations up to 150°C. Many polymers of different natures, sizes and topologies have been synthesized. The flow behavior of these polymers in both individual state in solution or in thermo-associative formulations was studied by rheology, thus enabling to determine the impact of these levers on the solutions properties as a function of temperature.

In the past 30 years, the discovery of capabilities of nucleic acids far beyond their well-known information-bearing capacity has profoundly influenced our understanding of these polymers. The discovery by the Cech and Altman labs that nucleic acids could perform catalytic functions, coupled with the Gold and Szostak groups’ demonstration of the de novo evolution of nucleic acids that bind arbitrary ligands, has resulted in a proliferation of newfound roles for these molecules. Nucleic acids have found utility in both engineered systems, such as aptamer therapeutics, as well as in newly appreciated roles in extant organisms, such as riboswitches. As a result of these discoveries, many have pondered the potential importance of the dual (catalytic and informational) roles of nucleic acids in early evolution. A high-yielding synthetic route for the nonenzymatic polymerization of nucleic acids, based on the aqueous self-assembly of their components, would provide a powerful tool in nucleic acid chemistry, with potential utility in prebiotic and contemporary nucleic acid systems alike – however, such a route remains elusive. In this thesis, I describe several steps towards such a synthetic route. In these systems, a nucleic-acid binding ligand drives the assembly of short DNA and RNA duplexes, promoting the production of long nucleic acid polymers, while suppressing the production of short, cyclic species. Additionally, the use of a reversible covalent linkage allows for the production of long polymers, as well as the incorporation of previously cyclized products into these polymers. I also report several explorations of novel base pairings, nucleic acid-ligand interactions, and nucleic acid-ion interactions that have informed our studies of self-assembling nucleic acid systems.

This thesis focuses on the design, synthesis and development of dynamic multivalent nanostructures such as supramolecular dendrimers, liposomes and gold-functionalized nanostructures. These structures can be used for drug delivery and molecular sensing applications. This thesis is divided into three parts: In part one, a general introduction to self-assembly, dynamic systems, metalligand exchange, nanostructured dendritic scaffolds, liposomes and gold nanostructures is given. In part two, a microwave approach is presented as an efficient method for the regioselective deuteration of bipyridine scaffolds. Dynamic systems based on transition metal-bipyridine coordination complexes were investigated. The compositional self-adaptation and kinetics of these dynamic systems were successfully assessed by ESI-MS. Based on this amphiphilic dendrimers/metallodendrimers were also designed and synthesized via  a convergent strategy. Their ability to self-assemble into supramolecular assemblies and their controlled disassembly was effectively demonstrated. In part three, two types of drug delivery systems based on dynamic multivalent nanostructures of glycodendrimers/metalloglycodendrimers and drugpresenting liposomes were developed. The dynamic self-assembly of these architectures into supramolecular nanostructures with site-specific functionality through interacting carbohydrate or cholesterol moieties was assessed. The host-guest interaction/encapsulation and controlled release with external stimuli were studied using a fluorescent probe, as well as selected drug molecules. The antibacterial property of the drug delivery systems was also evaluated, demonstrating an enhanced bactericidal activity. A new, rapid and simple approach for the functionalization of plasmonic gold nanostructured surfaces was also developed. The optical performance and light-specific sensitivity of the fluorescent probe on the resulting nanostructures were also presented. / <p>QC 20151119</p>

Les systèmes naturels ont montré l'intérêt de la multiplication des interactions pour une cible, permettant d'améliorer l'affinité et de moduler la spécificité de reconnaissance. Il est ainsi important pour des applications biologiques de concevoir des systèmes multivalents et biocompatibles. Le travail entreprit au cours de ce doctorat porte sur le développement de nouvelles méthodologies pour accéder à des systèmes multivalents originaux.Ainsi, nous avons conçu, par synthèse multi-étapes, une nouvelle plate-forme fonctionnalisée, basée sur un châssis α-PNA pour la reconnaissance multivalente d'oligonucléotides. Ce nouveau système peut potentiellement être impliqué dans la reconnaissance sélective multipoint d'ADN.En parallèle, nous avons préparé des clusters multivalents d'iminosucres sur des châssis peptidiques, construits à partir de ligations click sans métaux, pour l'inhibition enzymatique de glycosidases. En effet, des systèmes multivalents ont été récemment développés en tant qu'inhibiteurs de glycosidases. Cependant, leur méthodologie de synthèse repose quasiment exclusivement sur la ligation azoture-alcyne catalysée au cuivre, ce qui limite son application biologique en raison de sa toxicité. Nos travaux ont ainsi conduit à l'identification d'inhibiteurs efficaces d'α-mannosidases par une approche synthétique sans métaux.Dans le contexte de la vectorisation d'oligonucléotides, il existe un besoin de concevoir des systèmes dynamiques qui permettent un relargage contrôlé. Nous avons appliqué une stratégie d'auto-assemblage, par ligation click de type acylhydrazone, pour la génération in situ de clusters biomoléculaires à partir de châssis peptidiques et de ligands d'acides aminés modifiés. Etant donné le caractère dynamique de la ligation qui confère une adaptabilité au système, nous avons démontré que a) la présence d'une cible permet d'assister la formation des clusters par sélection de certains composants et b) l'ADN peut être relargué par échange de ligands. Cette technique efficace et rapide d'auto-assemblage de fragments a ensuite permis de réaliser un criblage pour sonder l'effet de l'architecture et de la valence sur la complexation. Ce projet a finalement conduit à l'identification de vecteurs efficace pour la transfection de siARN sur cellules.Enfin, dans un dernier projet, nous avons exploité diverses techniques orthogonales et chimiosélectives de ligations click dans le but de générer des nanostructures peptidiques. Deux cages ont ainsi été obtenues par la formation de ligations acylhydrazones et thiol-maléimides selon une approche one-pot.En résumé, ces travaux d'ingénierie et d'auto-assemblage de systèmes biomoléculaires multivalent ont permis le développement de méthodes innovantes pour répondre à des besoins d'actualité et permettre la construction de systèmes multivalents destinés à la reconnaissance d'oligonucléotides, la vectorisation et l'inhibition enzymatique. / Natural systems are inspiring in showing that the combination of multiple interactions enables improvement in binding affinity and selectivity for a target. Thus, the design of synthetic and biocompatible multivalent systems is of great importance for biological applications. The work described in this PhD thesis aims at developing novel methodologies for generating functional multivalent systems.In order to engineer multivalent systems for the recognition of oligonucleotides, we elaborated a multi-step synthesis of functionalized α-PNA scaffolds bearing side-groups. This new scaffold can potentially serve for the multi-point sequence-selective recognition of DNA.Multivalent nanoconstructs are emerging tools for enzyme inhibition. In this context, we prepared multivalent clusters of iminosugars – by metal-free click ligations on peptide scaffolds – as candidates for glycosidases inhibition. Although such enzyme inhibitors based on iminosugar clusters were recently reported, their synthesis relies almost exclusively on copper-catalyzed azide-alkyne cycloaddition, which notorious toxicity represents a serious limitation for biological applications. Our approach demonstrates that iminosugar clusters can be prepared in a metal-free fashion and exhibit strong multivalent effects for the inhibition of α-mannosidases. Multivalent biomolecular systems are also candidates for gene delivery application. In this context, the design of dynamic systems is of interest for achieving controlled release. We implemented a self-assembly strategy, using the acylhydrazone click ligation, for the in situ generation of biomolecular clusters starting from peptide scaffolds and modified amino acids building blocks. We showed that, whereas both compounds are ineffective for DNA complexation, the mixed system spontaneously expresses cationic clusters that effectively complex DNA. We further demonstrated that, given the dynamic character of the acylhydrazone ligation, the system is able to a) adapt to the presence of the DNA target by selecting the optimal building blocks for the cluster self-assembly, and b) trigger DNA release by component exchange. This modular and versatile self-assembly approach was further exploited to perform a fragments screening varying molecular structure and valency. Thereby, we identified new and effective vectors for the transfection of siRNA in living cells.The last project described in this manuscript deals with the generation of cage-type peptide nanoconstructs by using a set of orthogonal and chemoselective click ligations. Two cages, based on acylhydrazone ligation on one side and thiol-maleimide on the other, were obtained successfully in one-pot.In summary, this work has led to the development of novel methodologies for the engineering and self-assembly of multivalent biomolecular nanoconstructs for diverse biological applications such as oligonucleotide recognition, delivery and enzyme inhibition.

Biological systems have the incredible ability to accomplish uncommon chemical transformations with supreme delicacy. Many of those chemical transformations take place within the pocket of enzymes, which provide unique micro environment. From the quest of better understanding and to mimic such complex biological systems chemists have developed their own prototypes having well-defined cavity. To this end, in last few years many aesthetically elegant 3D discrete architectures have been devised by employing noncovalent interactions especially metal-ligand co-ordination and hydrogen bonding. Conversely, architectures based on purely covalent interactions are relatively limited in number, owing to the laborious traditional covalent synthesis, which involves multi-step synthetic protocols and irreversible covalent bond formations. Nevertheless, in recent times by utilizing dynamic covalent chemistry (DCC) several such organic 3D discrete ensembles have been developed with ease and efficiency from simple and easily accessible building blocks. Interestingly in most of such cases imine condensation reaction has been utilized due to easy formation and cleavage of the imine bonds in an efficient and reversible manner. However, it is quite surprising that even though the dynamic nature of imine bonds has been well established; self-sorting/self-selection process has been overlooked in organic cage systems. Self-sorting in biological realm is a well-established synthetic protocol. DNA double helix formation via hydrogen bonding between the complimentary base pairs is probably the best known example of biological self-sorting. Self-sorting process has the ability to discriminate self from non-self to achieve highly ordered architectures from within a random reaction mixture. The credit of self-sorting/self-selection process goes to the hidden ‘molecular instructions’ encrypted within the complimentary building blocks. The foremost objective of the present thesis work is to implement the self-sorting/self-selection protocol in organic cage formation by harnessing the dynamic imine chemistry. During the course of the investigation it has been observed that non-covalent interaction especially hydrogen bonding could manipulate the outcome of such a process. Besides that, selective formation of a single isomer of an organic cage from a reaction mixture of an unsymmetrical aldehyde and a flexible amine has been successfully achieved by simply fine tuning the geometric features (shape and size) of the reacting aldehyde. Such three-dimensional cages are well appreciated by the scientific community owing to their potential applications in anion sensing, catalysis and gas storage/separation. However, they have not been explored as sensors for nitroaromatic explosives. Therefore, at this juncture several fluorescent organic cages have been synthesized and their potential application as chemosensor for the nitroaromatics has been tested. Moreover, a new synthetic protocol has been introduced for the post-synthetic modification of organic cages. Chapter 1 covers a brief introduction about dynamic covalent chemistry with main emphasis on dynamic imine chemistry and its use in covalent cage synthesis. Moreover, this chapter accounts the very recent applications of such cage compounds in various fields such as a pours material for gas storage/separation, a molecular host for the stabilization of reactive species and for the recognition of ions or molecules. Chapter 2 describes first time ever achieved self-sorting process in three-dimensional purely organic cages. First of all, four different [3+2] cages were synthesized by treating two different triamines with two different dialdehydes separately, by employing dynamic imine chemistry. The formation of desired cages was ascertained by various spectroscopic techniques. When a mixture of all the four components (two aldehydes and two amines) was subjected to reaction, only two cages were found to form (Scheme 1) out of several equally probable possibilities, which suggest a high-fidelity self-recognition. The issue of partner preferences was further verified by transforming a non-self-sorted cage into a self-sorted cage by treating the former with appropriate triamine or dialdehyde. For an in-depth understanding on this subject, theoretical calculations (gas phase DFT) were carried out, which suggested that observed self-sorting is a thermodynamically governed process. Scheme 1. Self-sorting in organic imine cages through partner preferences. Chapter 3 focuses that supramolecular interaction especially hydrogen-boding could be a possible way to direct a self-sorting process operating in imine based organic cage systems. It is a well-accepted fact that in most of the cases self-sorting process operates owing to the difference in geometric features (shape and size) of the competing building blocks. Thus increasing similarity in geometric features would create the situation more complex. It is anticipated that in such circumstances H-bonding could have a decisive role in partner selection. In order to investigate this, four different dialdehydes (A, B, C and D) having similar geometric background were synthesized. These aldehydes upon treatment with flexible amine X were found to form three nanosocpic [3+2] organic cages (aldehyde C gave insoluble uncharacterized material). When a one-pot reaction of triamine X with mixture of all the four aldehydes was carried out, selective formation of cage B3X2 was observed (Scheme 2). Conversely, the same reaction in absence of aldehyde B resulted in the formation of mixture of products. Theoretical and experimental studies fully support the fact that the presence of hydroxyl moiety adjacent to the formyl group in aldehyde B has the key role in selective formation of cage B3X2 from a complex reaction mixture, in which there are numerous equally probable possibilities. Such remarkable selection was further examined by converting a non-hydroxy (non-preferred) cage into hydroxy cage B3X2 (preferred) by treating the former with aldehyde B. The role of the H-bond in self-sorting process of two dialdehydes and two triamines has been established. Furthermore, the possibility of cage–to- cage transformation through imine bond metathesis has also been addressed. Scheme 2. H-bond directed 15-fold (2+3) incomplete self-sorting in organic imine cages. Chapter 4 presents the investigation on the formation of single isomeric species of a [3+2] oligoimine cage from a reaction mixture of an unsymmetrical dialdehyde and a flexible triamine. So far, most of the reported organic cages are derived by symmetric building units. Asymmetric building blocks for the construction of such organic architectures are not the desirable choices, as they could lead to form mixture of isomeric cages. However, the asymmetric building blocks might form selectively one isomer only under the thermodynamic bias, which prefers the formation of one isomer over the other (s). In order to understand the factors that can direct such a process, three asymmetric dialdehydes (A, B and C) were synthesized and their reaction with a flexible amine X was carried out. Experimental outcomes suggested a striking difference in the abilities of isomer selection between aldehydes A/B and C. In case of aldehyde A/B selective formation of one oligoimine cage was observed, whereas aldehyde C led to form two isomeric oligoimine cages (Scheme 3). Experimental and theoretical findings have pointed out that the geometric features (shape and size) of the aldehyde play a decisive role in such isomer selection process. Scheme 3. Shape and size directed self-selection in organic imine cages. Part A of Chapter 5 describes the synthesis and characterization of a fluorescent organic cage compound and its application as a sensor for the detection of explosive picric acid (PA). Picric acid is known to be as explosive as trinitrotoluene (TNT) and one of the principle constituents of many unexplored landmines. Though there are several fluorescent polymers, metal-organic frameworks and small molecule based sensors have been devised in last few years but very little attention has been given towards selective and sensitive detection of picric acid. In this context desired organic cage compound 4 was synthesized by employing imine condensation between 4,4-diformyltriphenylamine (1) with 1,3,5-tris(aminomethyl)-2,4,6-trimethylbenzene (2) followed by reduction of the imine bonds (Scheme 4). This fluorescent nature of the cage in both the solid and solution has been utilized for the detection of nitroaromatic compounds (NACs). Among the various NACs tested it has been found that PA induces highest quenching of the initial fluorescence intensity of the cage solution. Furthermore, this cage has the ability to discriminate PA from other nitrophenolic compounds, such as 2,4-dinitrophenol (DNP) and 4-nitrophenol. In addition to solution phase detection cage 4 has also been successfully utilized for the solid phase detection of PA. The experimental results demonstrates that high sensitivity of the cage towards PA is attributed to the stronger ground state complex formation between the cage and PA as well as excitation v energy transfer (EET) process from protonated cage to the picrate. This represents the first report of a cage compound as a sensor for nitroaromatic compounds. Scheme 4. Synthesis of a fluorescent organic cage for the selective detection of picric acid. Part B of Chapter 5 reports a new synthetic methodology to decorate covalent organic cages post-synthetically, based on one-pot copper(I) catalyzed A3 coupling. A3-coupling is a three-component reaction between formaldehyde, secondary amine and terminal alkyne. In the present study selected organic cage 4 is furnished with six secondary amine moieties and thus it was allowed to react with 6 equiv. of formaldehyde and 6 equiv. of terminal alkyne in presence of CuI as a catalyst (Scheme 5). By employing this synthetic strategy parent cage 4 has been modified to cages 5a-c with appendages phenyl-, xylyl- and napthyl-actylenes. The resulting decorated cages were characterized by multinuclear NMR (1H and 13C), MALDI-TOF and FTIR spectroscopy. All the post-synthetically decorated cages were found to be fluorescent in nature and thus in v order to explore their potential use as a chemosensor for nitroaromatic compounds, cage 5a was tested. Experimental findings have suggested high selectivity of the cage towards nitroaromatic compounds. Interestingly, among the various nitroaromatics tested it has been observed that the cage is more sensitivity towards nitrophenolic compounds, whereas among the various nitrophenols tested, picric acid induced highest quenching. Scheme 5. Post-synthetic modification of an organic cage via cu+ catalyzed A3 coupling.

Directed assembly of molecular solids continues to attract widespread interest with its fundamental application in a wide range of commercial settings where control of the crystalline state of materials corresponds with product performance. These arenas include pharmaceuticals, personal care formulations, foods, paints and pigments and explosives. In recent times, the assembly of multicomponent organic systems has achieved considerable impetus with the widespread interest in co-crystal systems. However, cogent assembly (or engineering) of multicomponent materials is still in its infancy. Considerable advances in crystal design have been made through consideration of intermolecular ‘synthons’ – identifiable motifs utilising hydrogen bonds – but the translation of other molecular information (conformation, chirality, etc.) into solid state properties (e.g. long-range (translational) symmetry, crystal chirality) remains poorly understood. In this study, we have attempted to evaluate the influence of a chiral centre adjacent to molecular synthons to identify potential translation of information into the solid form. We have compared the co-crystallisation of nicotinamide with both the racemic mixture of malic acid against that with an enantiomerically pure form of the acid (L-malic acid). As well as DL-phenyllactic acid and L-phenyllactic acid. iii It is apparent that recognition between enantiomeric molecular forms play a significant role in the assembly of these systems. This mechanism can be considered independently from the H-bonding networks supporting the hetero-molecular interactions (e.g. acid-amide recognition). Discrimination and control of such interactions may play a role in transmitting chiral molecular information into solid state multi-component assemblies. In order to develop an understanding of co-crystal formation in chiral and achiral forms with intermolecular interactions, the CSD and crystal structures were obtained to do the analysis of how co-crystals pack. This study has also investigated the use of boronic acids. The aim of this study was to investigate the modification of the hydrogen bonding environment within the hydrogen bonded multi-component systems of boroxines. The study also attempted to determine how the starting materials drive the systems between the boronic acid co-crystal and the boroxine adduct.

Directed assembly of molecular solids continues to attract widespread interest with its fundamental application in a wide range of commercial settings where control of the crystalline state of materials corresponds with product performance. These arenas include pharmaceuticals, personal care formulations, foods, paints and pigments and explosives. In recent times, the assembly of multicomponent organic systems has achieved considerable impetus with the widespread interest in co-crystal systems. However, cogent assembly (or engineering) of multicomponent materials is still in its infancy. Considerable advances in crystal design have been made through consideration of intermolecular ‘synthons’ – identifiable motifs utilising hydrogen bonds – but the translation of other molecular information (conformation, chirality, etc.) into solid state properties (e.g. long-range (translational) symmetry, crystal chirality) remains poorly understood. In this study, we have attempted to evaluate the influence of a chiral centre adjacent to molecular synthons to identify potential translation of information into the solid form. We have compared the co-crystallisation of nicotinamide with both the racemic mixture of malic acid against that with an enantiomerically pure form of the acid (L-malic acid). As well as DL-phenyllactic acid and L-phenyllactic acid. iii It is apparent that recognition between enantiomeric molecular forms play a significant role in the assembly of these systems. This mechanism can be considered independently from the H-bonding networks supporting the hetero-molecular interactions (e.g. acid-amide recognition). Discrimination and control of such interactions may play a role in transmitting chiral molecular information into solid state multi-component assemblies. In order to develop an understanding of co-crystal formation in chiral and achiral forms with intermolecular interactions, the CSD and crystal structures were obtained to do the analysis of how co-crystals pack. This study has also investigated the use of boronic acids. The aim of this study was to investigate the modification of the hydrogen bonding environment within the hydrogen bonded multi-component systems of boroxines. The study also attempted to determine how the starting materials drive the systems between the boronic acid co-crystal and the boroxine adduct.