Pathway-dependent Metallosupramolecular Polymerization Regulated by Ligand Geometry.

Understanding structure/property correlations in self-assembly is a key but challenging requirement for developing functional materials. Herein, we explore the importance of ligand geometry to tune photophysical properties (MMLCT vs. MLCT excited states) and self-assembly pathways in metallosupramolecular polymerization. To this end, we have designed two hydrophobic Pt(II) complexes, 1 and 2, containing a π-extended bidentate bipyridine ligand with different substitution pattern, resulting in different molecular geometries (linear vs V-shaped). Detailed comparative studies revealed significant differences for both complexes in terms of their photophysical properties and self-assembly pathways in non-polar media. The V-shaped topology of 1 enables facile face-to-face molecular stacking with a certain curvature leading to luminescent spherical assemblies exhibiting MMLCT states and short Pt···Pt contacts via a single-step cooperative pathway. On the other hand, the higher preorganized linear topology of complex 2 induces a two-step competitive self-assembly process leading to the formation of one-dimensional supramolecular polymers with slipped packing and MLCT-originated emission. Our findings broaden the monomer scope for supramolecular polymerization and provide design guidelines for the realization of luminescent supramolecular assemblies.

Complex Pathways Drive Pluripotent Fmoc-Leucine Self-Assemblies.

Nature uses complex self-assembly pathways to access distinct functional non-equilibrium self-assemblies. This remarkable ability to steer same set of biomolecules into different self-assembly states is done by avoiding thermodynamic pit. In synthetic systems, on demand control over 'Pathway Complexity' to access self-assemblies different from equilibrium structures remains challenging. Here we show versatile non-equilibrium assemblies of the same monomer via alternate assembly pathways. The assemblies nucleate using non-classical or classical nucleation routes into distinct metastable (transient hydrogels), kinetic (stable hydrogels) and thermodynamic structures [(poly)-crystals and 2D sheets]. Initial chemical and thermal inputs force the monomers to follow different assembly pathways and form soft-materials with distinct molecular arrangements than at equilibrium. In many cases, equilibrium structures act as thermodynamic sink which consume monomers from metastable structures giving transiently formed materials. This dynamics can be tuned chemically or thermally to slow down the dissolution of transient hydrogel, or skip the intermediate hydrogel altogether to reach final equilibrium assemblies. If required this metastable state can be kinetically trapped to give strong hydrogel stable over days. This method to control different self-assembly states can find potential use in similar biomimetic systems to access new materials for various applications.

Noncovalent Catalyst-cum-Inhibitor Directed Supramolecular Pathway Selection and Asymmetry Amplification by Aggregate Cross-Nucleation.

The key to any controlled supramolecular polymerization (CSP) process lies in controlling the nucleation step, which is typically achieved by sequestering monomers in a kinetically trapped state. However, kinetic traps that are shallow cannot prevent spontaneous nucleation, thus limiting the applicability of the CSP in such systems. We use a molecular additive to overcome this limitation by modifying the energy landscape of a competitive self-assembly process and increasing the kinetic stability of an otherwise short-lived trap state. The additive achieves this by simultaneously catalyzing OFF-pathway nucleation and inhibiting ON-pathway aggregation. In the process, it guides the molecular assembly exclusively toward the OFF-pathway aggregate analogue. The mechanisms of OFF-pathway catalysis and ON-pathway inhibition are elucidated. By specifically targeting the nucleation step, it was possible to achieve pathway selection at an extremely low additive-to-monomer ratio of 1:100. The generality of our approach is also demonstrated for other related molecular systems. Finally, removing the additive triggers the cross-nucleation of the ON-pathway aggregate on the surface of a less stable, OFF-pathway aggregate analogue. The resultant supramolecular polymer not only exhibits a more uniform morphology but more importantly, a marked improvement in the structural order that leads to an amplification of chiral asymmetry and a high absorption dissymmetry factor (gAbs) of ∼0.05.

Control of Kinetic Pathways toward Supramolecular Chiral Polymorphs for Tunable Circularly Polarized Luminescence.

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788-805 nm and g-factors between -4.2×10-2 and -5.1×10-2.

Effect of chirality in the supramolecular polymerization of N-annulated perylenediimides: Cancelling pathway complexity.

Herein, the synthesis of two chiral NPBIs, (S)-1 and (R)-1, is reported and their self-assembling features investigated. The reported NPBIs form chiral supramolecular polymers with a rich dichroic pattern by the π-stacking of the aromatic backbones and the formation of an array of H-bonds between the amide functional groups. Furthermore, the peripheral 3,4,5-trialkoxy benzamide groups can form seven-membered pseudocycles by the intramolecular H-bonding interaction between the NH of the peripheral amides and one of the carbonyls of the imide units thus yielding a kinetically controlled self-assembly process. Unlike achiral NPBI 1, that has been reported to form up to four supramolecular polymorphs, the reported chiral NPBIs form only a J-type aggregated species. The results presented herein reveal how subtle changes exert an enormous influence on the supramolecular polymerization outcome.

Revealing Pathway Complexity and Helical Inversion in Supramolecular Assemblies Through Solvent-Induced Radical Disparities.

New insights are raised to interpret pathway complexity in the supramolecular assembly of chiral triarylamine tris-amide (TATA) monomer. In cosolvent systems, the monomer undergoes entirely different assembly processes depending on the chemical feature of the two solvents. Specifically, 1,2-dichloroethane (DCE) and methylcyclohexane (MCH) cosolvent trigger the cooperative growth of monomers with M helical arrangement, and hierarchical thin nanobelts are further formed. But in DCE and hexane (HE) combination, a different pathway occurs where monomers go through isodesmic growth to generate twisted nanofibers with P helical arrangement. Moreover, the two distinct assemblies exhibit opposite excited-state chirality. The driving force for both assemblies is the formation of intermolecular hydrogen bonds between amide moieties. However, the mechanistic investigation indicates that radical and neutral triarylamine species go through distinct assembly phases by changing solvent structures. The neutralization of radicals in MCH plays a critical role in pathway complexity, which significantly impacts the overall supramolecular assembly process, giving rise to inversed supramolecular helicity and distinct morphologies. This differentiation in pathways affected by radicals provides a new approach to manipulate chiral supramolecular assembly process by facile solvent-solute interactions.

Seed-Induced Living Two-Dimensional (2D) Supramolecular Polymerization in Water: Implications on Protein Adsorption and Enzyme Inhibition.

In biological systems, programmable supramolecular frameworks characterized by coordinated directional non-covalent interactions are widespread. However, only a small number of reports involve pure water-based dynamic supramolecular assembly of artificial π-amphiphiles, primarily due to the formidable challenge of counteracting the strong hydrophobic dominance of the π-surface in water, leading to undesired kinetic traps. This study reveals the pathway complexity in hydrogen-bonding-mediated supramolecular polymerization of an amide-functionalized naphthalene monoimide (NMI) building block with a hydrophilic oligo-oxyethylene (OE) wedge. O-NMI-2 initially produced entropically driven, collapsed spherical particles in water (Agg-1); however, over a span of 72 h, these metastable Agg-1 gradually transformed into two-dimensional (2D) nanosheets (Agg-2), favoured by both entropy and enthalpy contributions. The intricate self-assembly pathways in O-NMI-2 enable us to explore seed-induced living supramolecular polymerization (LSP) in water for controlled synthesis of monolayered 2D assemblies. Furthermore, we demonstrated the nonspecific surface adsorption of a model enzyme, serine protease α-Chymotrypsin (α-ChT), and consequently the enzyme activity, which could be regulated by controlling the morphological transformation of O-NMI-2 from Agg-1 to Agg-2. We delve into the thermodynamic aspects of such shape-dependent protein-surface interactions and unravel the impact of seed-induced LSP on temporally controlling the catalytic activity of α-ChT.

The calculus of codes - From entropy, complexity, and information to life.

Exploring the core components that define living systems and their operational mechanisms within emerging biological entities is a complex endeavor. In the realm of biological systems literature, the terms matter, energy, information, complexity, and entropy are frequently referenced. However, possessing these concepts alone does not guarantee a comprehensive understanding or the ability to reconstruct the intricate nature of life. This study aims to illuminate the trajectory of these organic attributes, presenting a theoretical framework that delves into the integrated role of these concepts in biology. We assert that Code Biology serves as a pivotal steppingstone for unraveling the mechanisms underlying life. Biological codes (BCs) emerge not only from the interplay of matter and energy but also from Information. Contrary to deriving information from the former elements, we propose that information holds its place as a fundamental physical aspect. Consequently, we propose a continuum perspective called Calculus of Fundamentals involving three fundamentals: Matter, Energy, and Information, to depict the dynamics of BCs. To achieve this, we emphasize the necessity of studying Entropy and Complexity as integral organic descriptors. This perspective also facilitates the introduction of a mathematical theoretical framework that aids in comprehending continuous changes, the driving dynamics of biological fundamentals. We posit that Energy, Matter, and Information constitute the essential building blocks of living systems, and their interactions are governed by Entropy and Complexity analyses, redefined as biological descriptors. This interdisciplinary perspective of Code Biology sheds light on the intricate interplay between the controversial phenomenon of life and advances the idea of constructing a theory rooted in information as an organic fundamental.

Sterically Allowed H-type Supramolecular Polymerizations.

The functionalization of π-conjugated scaffolds with sterically demanding substituents is a widely used tactic to suppress cofacial (H-type) stacking interactions, which may even inhibit self-assembly. Contrary to expectations, we demonstrate herein that increasing steric effects can result in an enhanced thermodynamic stability of H-type supramolecular polymers. In our approach, we have investigated two boron dipyrromethene (BODIPY) dyes with bulky phenyl (2) and mesityl (3) meso-substituents and compared their self-assembly in nonpolar media with that of a parent meso-methyl BODIPY 1 lacking bulky groups. While the enhanced steric demand induces pathway complexity, the superior thermodynamic stability of the H-type pathways can be rationalized in terms of additional enthalpic gain arising from intermolecular C-H⋅⋅⋅F-B interactions of the orthogonally arranged aromatic substituents, which overrule their inherent steric demand. Our findings underline the importance of balancing competing non-covalent interactions in self-assembly.

Kinetic Delay in Cooperative Supramolecular Polymerization by Redefining the Trade-Off Relationship between H-Bonds and Van der Waals/π-π Stacking Interactions.

We here present how rebalancing the interplay between H-bonds and dispersive forces (Van der Waals/π-π stacking) may induce or not the generation of kinetic metastable states. In particular, we show that extending the aromatic content and favouring the interchain VdW interactions causes a delay into the cooperative supramolecular polymerization of a new family of toluene bis-amide derivatives by trapping the metastable inactive state.

Pathway Control of π-Conjugated Supramolecular Polymers by Incorporating Donor-Acceptor Functionality.

Controlling the nanoscale orientation of π-conjugated systems remains challenging due to the complexity of multiple energy landscapes involved in the supramolecular assembly process. In this study, we have developed an effective strategy for programming the pathways of π-conjugated supramolecular polymers, by incorporating both electron-rich methoxy- or methanthiol-benzene as donor unit and electron-poor cyano-vinylenes as acceptor units on the monomeric structure. It leads to the formation of parallel-stacked supramolecular polymers as the metastable species through homomeric donor/acceptor packing, which convert to slip-stacked supramolecular polymers as the thermodynamically stable species facilitated by heteromeric donor-acceptor packing. By further investigating the external seed-induced kinetic-to-thermodynamic transformation behaviors, our findings suggest that the donor-acceptor functionality on the seed structure is crucial for accelerating pathway conversion. This is achieved by eliminating the initial lag phase in the supramolecular polymerization process. Overall, this study provides valuable insights into designing molecular structures that control aggregation pathways of π-conjugated nanostructures.

Temperature-Controlled Pathway Complexity in Self-Assembly of Perylene Diimide-Polydiacetylene Supramolecule.

Self-assembly process represents one of the most powerful and efficient methods for designing functional nanomaterials. For generating optimal functional materials, understanding the pathway complexity during self-assembly is essential, which involves the aggregation of molecules into thermodynamically or kinetically favored pathways. Herein, a functional perylene diimide (PDI) derivative by introducing diacetylene (DA) chains (PDI-DA) is designed. Temperature control pathway complexity with the evolution of distinct morphology for the kinetic and thermodynamic product of PDI-DA is investigated in detail. A facile strategy of UV-induced polymerization is adopted to trap and capture metastable kinetic intermediates to understand the self-assembly mechanism. PDI-DA showed two kinetic intermediates having the morphology of nanosheets and nanoparticles before transforming into the thermodynamic product having fibrous morphology. Spectroscopic studies revealed the existence of distinct H- and J-aggregates for kinetic and thermodynamic products respectively. The polymerized fibrous PDI-DA displayed reversible switching between J-aggregate and H-aggregate.

Modulating the Differentiation of Kinetically Controlled Supramolecular Polymerizations through the Alkyl Bridge Length.

The synthesis and self-assembling features of N-annulated perylenebisimides (N-PBIs) 2-4 are reported and compared with the complex self-assembly of N-PBI 1. The studies presented herein demonstrate that increasing the length of the alkyl spacer separating the central aromatic core of the dye and the peripheral side chains cancels the differentiation on the corresponding supramolecular polymerization. Thus, only 2 is able to form two different supramolecular polymorphs. The formation of kinetically trapped monomeric species is observed for all the N-PBIs 2-4. These metastable species, constituted by intramolecularly H-bonded pseudocycles of 7, 8, 9, or 10 members for compounds 1, 2, 3, and 4, respectively, provoke kinetically controlled supramolecular polymerizations that can be accelerated by the addition of seeds. The results presented herein shed light on the intricate process of differentiation in self-assembly.

Luminescence and Length Control in Nonchelated d8 -Metallosupramolecular Polymers through Metal-Metal Interactions.

Supramolecular polymers (SPs) of d8 transition metal complexes have received considerable attention by virtue of their rich photophysical properties arising from metal-metal interactions. However, thus far, the molecular design is restricted to complexes with chelating ligands due to their advantageous preorganization and strong ligand fields. Herein, we demonstrate unique pathway-controllable metal-metal-interactions and remarkable 3 MMLCT luminescence in SPs of a non-chelated PtII complex. Under kinetic control, self-complementary bisamide H-bonding motifs induce a rapid self-assembly into non-emissive H-type aggregates (1A). However, under thermodynamic conditions, a more efficient ligand coplanarization leads to superiorly stabilized SP 1B with extended Pt⋅⋅⋅Pt interactions and remarkably long 3 MMLCT luminescence (τ77 K =0.26 ms). The metal-metal interactions could be subsequently exploited to control the length of the emissive SPs using the seeded-growth approach.

Tracing Eukaryotic Ribosome Biogenesis Factors Into the Archaeal Domain Sheds Light on the Evolution of Functional Complexity.

Ribosome assembly is an essential and carefully choreographed cellular process. In eukaryotes, several 100 proteins, distributed across the nucleolus, nucleus, and cytoplasm, co-ordinate the step-wise assembly of four ribosomal RNAs (rRNAs) and approximately 80 ribosomal proteins (RPs) into the mature ribosomal subunits. Due to the inherent complexity of the assembly process, functional studies identifying ribosome biogenesis factors and, more importantly, their precise functions and interplay are confined to a few and very well-established model organisms. Although best characterized in yeast (Saccharomyces cerevisiae), emerging links to disease and the discovery of additional layers of regulation have recently encouraged deeper analysis of the pathway in human cells. In archaea, ribosome biogenesis is less well-understood. However, their simpler sub-cellular structure should allow a less elaborated assembly procedure, potentially providing insights into the functional essentials of ribosome biogenesis that evolved long before the diversification of archaea and eukaryotes. Here, we use a comprehensive phylogenetic profiling setup, integrating targeted ortholog searches with automated scoring of protein domain architecture similarities and an assessment of when search sensitivity becomes limiting, to trace 301 curated eukaryotic ribosome biogenesis factors across 982 taxa spanning the tree of life and including 727 archaea. We show that both factor loss and lineage-specific modifications of factor function modulate ribosome biogenesis, and we highlight that limited sensitivity of the ortholog search can confound evolutionary conclusions. Projecting into the archaeal domain, we find that only few factors are consistently present across the analyzed taxa, and lineage-specific loss is common. While members of the Asgard group are not special with respect to their inventory of ribosome biogenesis factors (RBFs), they unite the highest number of orthologs to eukaryotic RBFs in one taxon. Using large ribosomal subunit maturation as an example, we demonstrate that archaea pursue a simplified version of the corresponding steps in eukaryotes. Much of the complexity of this process evolved on the eukaryotic lineage by the duplication of ribosomal proteins and their subsequent functional diversification into ribosome biogenesis factors. This highlights that studying ribosome biogenesis in archaea provides fundamental information also for understanding the process in eukaryotes.

Externally Regulated Specific Molecular Recognition Driven Pathway Selectivity in Supramolecular Polymerization.

This article reveals 4-dimethylaminopyridine (DMAP) regulated pathway selectivity in the supramolecular polymerization of a naphthalene-diimide derivative (NDI-1), appended with a carboxylic acid group. In decane, NDI-1 produces ill-defined aggregate (Agg-1) due to different H-bonding motifs of the -COOH group. With one mole equivalent DMAP, the NDI-1/DMAP complex introduces new nucleation condition and exhibits a cooperative supramolecular polymerization producing J-aggregated fibrillar nanostructure (Agg-2). With 10 % DMAP and fast cooling (10 K/min), similar nucleation and open chain H-bonding with the free monomer in an anti-parallel arrangement produces identical J-aggregate (Agg-2a). With 2.5 % DMAP and slow cooling (1 K/min), a distinct nucleation and supramolecular polymerization pathway emerge leading to the thermodynamically controlled Agg-3 with face-to-face stacking and 2D-morphology. Slow cooling with 5-10 % DMAP produces a mixture of Agg-2a and Agg-3. Computational modelling studies provide valuable insights into the internal order and the pathway complexity.

Energetics of Competing Chiral Supramolecular Polymers.

Chirality can have unexpected consequences including on properties other than spectroscopic. We show herein that a racemic mixture of bis-urea stereoisomers forms thermodynamically stable supramolecular polymers that result in a more viscous solution than for the pure stereoisomer. The origin of this macroscopic property was probed by characterizing the structure and stability of the assemblies. Both racemic and non-racemic bis-urea stereoisomers form two competing helical supramolecular polymers in solution: a double and a single helical structure at low and high temperature, respectively. The transition temperature between these assemblies, as probed by spectroscopic and calorimetric analyses, is strongly influenced by the composition (by up to 70 °C). A simple model that accounts for the thermodynamics of this system, indicates that the stereochemical defects (chiral mismatches and helix reversals) affect much more the stability of single helices. Therefore, the heterochiral double helical structure predominates over the single helical structure (whilst the opposite holds for the homochiral structures), which explains the aforementioned higher viscosity of the racemic bis-urea solution. This rationale constitutes a new basis to tune the macroscopic properties of the increasing number of supramolecular polymers reported to exhibit competing chiral nanostructures.

Exploiting Reaction-Diffusion Conditions to Trigger Pathway Complexity in the Growth of a MOF.

Coordination polymers (CPs), including metal-organic frameworks (MOFs), are crystalline materials with promising applications in electronics, magnetism, catalysis, and gas storage/separation. However, the mechanisms and pathways underlying their formation remain largely undisclosed. Herein, we demonstrate that diffusion-controlled mixing of reagents at the very early stages of the crystallization process (i.e., within ≈40 ms), achieved by using continuous-flow microfluidic devices, can be used to enable novel crystallization pathways of a prototypical spin-crossover MOF towards its thermodynamic product. In particular, two distinct and unprecedented nucleation-growth pathways were experimentally observed when crystallization was triggered under microfluidic mixing. Full-atom molecular dynamics simulations also confirm the occurrence of these two distinct pathways during crystal growth. In sharp contrast, a crystallization by particle attachment was observed under bulk (turbulent) mixing. These unprecedented results provide a sound basis for understanding the growth of CPs and open up new avenues for the engineering of porous materials by using out-of-equilibrium conditions.

The Mastigamoeba balamuthi Genome and the Nature of the Free-Living Ancestor of Entamoeba.

The transition of free-living organisms to parasitic organisms is a mysterious process that occurs in all major eukaryotic lineages. Parasites display seemingly unique features associated with their pathogenicity; however, it is important to distinguish ancestral preconditions to parasitism from truly new parasite-specific functions. Here, we sequenced the genome and transcriptome of anaerobic free-living Mastigamoeba balamuthi and performed phylogenomic analysis of four related members of the Archamoebae, including Entamoeba histolytica, an important intestinal pathogen of humans. We aimed to trace gene histories throughout the adaptation of the aerobic ancestor of Archamoebae to anaerobiosis and throughout the transition from a free-living to a parasitic lifestyle. These events were associated with massive gene losses that, in parasitic lineages, resulted in a reduction in structural features, complete losses of some metabolic pathways, and a reduction in metabolic complexity. By reconstructing the features of the common ancestor of Archamoebae, we estimated preconditions for the evolution of parasitism in this lineage. The ancestor could apparently form chitinous cysts, possessed proteolytic enzyme machinery, compartmentalized the sulfate activation pathway in mitochondrion-related organelles, and possessed the components for anaerobic energy metabolism. After the split of Entamoebidae, this lineage gained genes encoding surface membrane proteins that are involved in host-parasite interactions. In contrast, gene gains identified in the M. balamuthi lineage were predominantly associated with polysaccharide catabolic processes. A phylogenetic analysis of acquired genes suggested an essential role of lateral gene transfer in parasite evolution (Entamoeba) and in adaptation to anaerobic aquatic sediments (Mastigamoeba).

Influence of the Z/E Isomerism on the Pathway Complexity of a Squaramide-Based Macrocycle.

The rising interest on pathway complexity in supramolecular polymerization has prompted the finding of novel monomer designs able to stabilize kinetically trapped species and generate supramolecular polymorphs. In the present work, the exploitation of the Z/E (geometrical) isomerism of squaramide (SQ) units to produce various self-assembled isoforms and complex supramolecular polymerization pathways in methylcyclohexane/CHCl3 mixtures is reported for the first time. This is achieved by using a new bissquaramidic macrocycle (MSq) that self-assembles into two markedly different thermodynamic aggregates, AggA (discrete cyclic structures) and AggB (fibrillar structures), depending on the solvent composition and concentration. Remarkably, UV-vis, 1 H NMR, and FT-IR experiments together with quantum-chemical calculations indicate that these two distinct aggregates are formed via two different hydrogen bonding patterns (side-to-side in AggA and head-to-tail in AggB) due to different conformations in the SQ units (Z,E in AggA and Z,Z in AggB). The ability of MSq to supramolecularly polymerize into two distinct aggregates is utilized to induce the kinetic-to-thermodynamic transformation from AggA to AggB, which occurs via an on-pathway mechanism. It is believed that this system provides new insights for the design of potential supramolecular polymorphic materials by using squaramide units.