Chemical Building Blocks Research Articles

Ketonization of Valeric Acid to 5‐Nonanone Over Metal Oxides Catalysts

AbstractValeric acid (VA), readily obtainable in the biorefinery from sugary biomass streams, can be upgraded to 5‐nonanone, a versatile chemical building block with numerous applications. This study investigates the performance of nine metal oxide catalysts (SnO2, SiO2, Y2O3, CeO2, ZrO2, TiO2, La2O3, Cr2O3, and Al2O3) in the gas‐phase ketonization of VA to 5‐nonanone in the 350–450 °C range. The screening reveals a correlation between the metal oxides lattice energy and their catalytic activity for valeric acid ketonization. ZrO2, TiO2, and La2O3, characterized by high lattice energy, demonstrate the highest catalytic activity, whereas Y2O3, SnO2, and SiO2, showing low lattice energy, are barely active. However, exceptions to this trend were observed: Cr2O3 and Al2O3 displayed poor catalytic performance despite their elevated lattice energy. The comprehensive characterization of the catalysts, encompassing XRD, N2‐physisorption, NH3‐TPD, and CO2‐TPD analyses, has unveiled the crucial role of important parameters including acid–base properties in addition to lattice energy. Only oxides showing amphoteric properties can catalyze the reaction effectively. Interestingly, low‐lattice energy and amphoteric oxides such as SnO2 (showing poor performance) become significantly active at higher temperature (500 °C). Analysis of by‐products by online GCMS and spent catalyst characterization indicated that in this case the ketonization mechanism changed from the so‐called surface mechanism to the so‐called bulk mechanism.

Bioconversion of Food and Green Waste into Valuable Compounds Using Solid-State Fermentation in Nonsterile Conditions.

Agro-industrial residues have transitions from being an environmental problem to being a cost-effective source of biopolymers and value-added chemicals. However, the efficient extraction of the desired products from these residues requires pretreatments. Fungal biorefinery is a fascinating approach for the biotransformation of raw materials into multiple products in a single batch. In this study, the ability of Trichoderma asperellum R to convert fruit scrap and green waste into value-added chemicals was tested in solid-state and in nonsterile conditions. A solid-state fermentation protocol for a tray bioreactor was developed using spawn as the inoculum for nonsterile substrates. T. asperellum R drove the fermentation of both substrates, shaping the metabolites that were enriched in the secondary plant metabolites. Strain R showed cellulase activity only when inoculated on fruit scraps, resulting in increased amounts of polysaccharides in the crude extract. This extract was also enriched in vanillic acid and limonoid, which are intriguing compounds due to the increasing interest in their potential as biological nitrification inhibitors or food additives. Finally, trimethoxybenzaldehyde, an interesting chemical building block, was identified in the extracts of the Trichoderma-guided fermentation. The overall results showed that the application of T. asperellum R has potential as a driver to facilitate the extraction of bioactive substances from nonsterile recalcitrant substrates.

Platform for Aldehyde and Ketone Quantitation Using Surface-Enhanced Raman Spectroscopy.

Colorimetric methods for aldehyde and ketone analyses are plagued by interferences. Each aldehyde or ketone generates a blue color, but with a different reaction coefficient. It is, therefore, not possible to differentiate these compounds from a single test. By using surface-enhanced Raman spectroscopy, we demonstrate unique fingerprints for each reaction product, enabling aldehyde and ketone speciation. With the further addition of an isotopologue internal standard, we demonstrate aldehyde and ketone quantification at levels lower than those possible with colorimetric techniques. This method paves the way for a powerful and practical tool for analyzing these crucial chemical building blocks.

Synergistic photobiocatalysis for enantioselective triple radical sorting.

Multicomponent reactions - those where three or more substrates combine into a product - have been highly useful in rapidly building chemical building blocks of increased complexity4, but achieving this enzymatically has remained rare.5 This limitation primarily arises because an enzyme's active site is not typically set up to address multiple substrates, especially in cases involving multiple radical intermediates6. Recently, chemical catalytic radical sorting has emerged as an enabling strategy for a variety of useful reactions7,8. However, making such processes enantioselective is highly challenging due to the inherent difficulty in the stereochemical control of radicals9. Here, we repurpose a thiamine-dependent enzyme10,11 through directed evolution, combine it with photoredox catalysis, to achieve a photobiocatalytic enantioselective three-component radical cross-coupling. This approach combines three readily available starting materials - aldehydes, α-bromo-carbonyls and alkenes - to give access to enantioenriched ketone products. Mechanistic investigations provide insights into how this dual photo-/enzyme system precisely directs the three distinct radicals involved in the transformation, unlocking new enzyme reactivity. Our approach has achieved exceptional stereoselectivity, with 25 out of 33 examples achieving ≥97% enantiomeric excess.

Proline Analogues in Drug Design: Current Trends and Future Prospects.

Proline analogues are versatile chemical building blocks that enable modular construction of small-molecule drugs and pharmaceutical peptides. Over the past 15 years, the FDA has approved over 15 drugs containing proline analogues in their structures, five in the last three years alone (daridorexant, trofinetide, nirmatrelvir, rezafungin, danicopan). This perspective offers an analysis of the most common types of proline analogues currently trending in drug design. We focus on examples of fluoroprolines, α-methylproline, bicyclic proline analogues, and aminoprolines, while also highlighting proline analogues that remain underrepresented. We supplement our analysis with physicochemical information regarding the specific molecular properties of these moieties. Additionally, we discuss several intriguing cases where nonproline residues were replaced with proline analogues as a strategy to eliminate unwanted hydrogen bond donor sites. In conclusion, we present some suggestions for the future exploration of this promising class of molecular entities in drug discovery.

Improvement of succinate production from methane by combining rational engineering and laboratory evolution in Methylomonas sp. DH-1

Recently, methane has been considered a next-generation carbon feedstock due to its abundance and it is main component of shale gas and biogas. Methylomonas sp. DH-1 has been evaluated as a promising industrial bio-catalyst candidate. Succinate is considered one of the top building block chemicals in the agricultural, food, and pharmaceutical industries. In this study, succinate production by Methylomonas sp. DH-1 was improved by combining adaptive laboratory evolution (ALE) technology with genetic engineering in the chromosome of Methylomonas sp. DH-1, such as deletion of bypass pathway genes (succinate dehydrogenase and succinate semialdehyde dehydrogenase) or overexpression of genes related with succinate production (citrate synthase, pyruvate carboxylase and phosphoenolpyruvate carboxylase). Through ALE, the maximum consumption rate of substrate gases (methane and oxygen) and the duration maintaining high substrate gas consumption rates was enhanced compared to those of the parental strain. Based on the improved methane consumption, cell growth (OD600) increased more than twice, and the succinate titer increased by ~ 48% from 218 to 323 mg/L. To prevent unwanted succinate consumption, the succinate semialdehyde dehydrogenase gene was deleted from the genome. The first enzyme of TCA cycle (citrate synthase) was overexpressed. Pyruvate carboxylase and phosphoenolpyruvate carboxylase, which produce oxaloacetate, a substrate for citrate synthase, were also overproduced by a newly identified strong promoter. The new strong promoter was screened from RNA sequencing data. When these modifications were combined in one strain, the maximum titer (702 mg/L) was successfully improved by more than three times. This study demonstrates that successful enhancement of succinic acid production can be achieved in methanotrophs through additional genetic engineering following adaptive laboratory evolution.

Electrochemical conversion of biomass derivatives to value-added chemicals: A review

Countless efforts have been dedicated to shifting from fossil-to bio-based resources, including the conversion of biomass derivatives into high-value building-block chemicals using various catalytic processes. In particular, electrochemical conversion is a remarkable process when considering biomass as a renewable resource and when applying renewable energy. As typical promising derivatives, 5-hydroxymethylfurfural, methanol, and sugars have been extensively investigated to date on a laboratory scale via electrochemical conversion to obtain valuable chemicals such as 2,5-furan dicarboxylic acid, 2,5-di(hydroxymethyl)furan, formic acid, gluconic acid, and xylitol. This review focuses on the electroconversion of biomass derivatives to high-value-added products. In particular, the catalyst activity, stability, and selectivity for the desired products, reaction mechanisms, and operating conditions of the electrocatalytic process are summarized and discussed. The review also addresses the challenges in the development of electrocatalysts for the electroconversion of biomass derivatives while avoiding side reactions to reduce the separation and purification processes. This study is expected to guide future developments in this field.

Solar Selective Photooxidation of Veratryl Alcohol by Suppression of Reactive Oxygen Species Through Band Modulation in the BiOI/Bi4Ti3O12 Heterojunction.

Lignin valorization through heterogeneous photocatalysis is a promising pathway for obtaining value-added products, including chemical building blocks, biofuels, etc. However, several challenges still demand attention and resolution in this field. One of the key parameters in the heterogeneous photocatalytic process is the synthesis of efficient photocatalysts that can accomplish efficient and selective reactions. Selective conversion of lignin can be achieved by using heterojunction photocatalysts which can efficiently separate charge carriers' and promote selective reactions by band structure modulation. This work details a straightforward approach for synthesizing heterojunction photocatalysts based on Bi4Ti3O12 and BiOI involving the hydrothermal and co-precipitation methods. Additionally, the synthesized composites were employed in the selective oxidation of veratryl alcohol, a lignin-derived model compound, to produce high-value-added veratraldehyde. The experimental results showed that the BiOI/Bi4Ti3O12 heterojunction (12.5 mol % BiOI) showed superior activity with a veratraldehyde yield of 5.4 and 27.2 times higher than those of Bi4Ti3O12 and BiOI, respectively. The mechanistic studies revealed that the improved activity and selectivity were due to the enhanced charge carriers' separation and the suppression of reactive oxygen species formation through modulation of band structure. This study allows a green approach to lignin-derived biomass valorization to obtain high-value chemicals.

Efficient corn stover-derived metal-supported biochar catalyst for hydrogenation of xylose to xylitol

Xylitol, one of the top twelve chemical building blocks, is commercially synthesized through the xylose hydrogenation reaction using a metal catalyst. Biochar has emerged as an eco-efficient catalyst support material. In this study, biochar derived from corn stover (BCS) was first used as a metal catalyst support material for xylose hydrogenation into xylitol. The catalyst was prepared by carbonizing corn stover (CS), impregnating the resulting biochar with metal, and reducing the metal-impregnated BCS. The catalyst characteristics were comprehensively explored. The Ru/BCS catalyst was employed in xylose conversion to xylitol at different process temperatures (100 – 160 °C), retention times (3 – 12 h), H2 pressures (2 – 5 MPa), and Ru contents (1 – 5 %). The highest xylitol yield (87.0 wt.%) and selectivity (91.6 %) were derived at 120 °C for 6 h under 4 MPa H2 using 5 % Ru. Interestingly, the Ru/BCS catalyst showed high stability under the promising process condition. Additionally, xylitol production from hydrolysates enriched with CS xylose was subsequently explored. On the other hand, the catalyst characterization results revealed that the superior catalytic efficiency of 5Ru/BCS was mainly due to the metal nanoparticles embedded in the biochar. Additionally, BCS proved to be an outstanding support material for a bimetallic hydrogenation catalyst (Ru-Ni/BCS). Therefore, these results indicate that BCS can be a competitive support material for metal hydrogenation catalysts, enhancing environmental friendliness and potentially being employed in industrial-scale xylitol production.

SYNTHESIS OF N-BENZYLPIPERIDINE-4-ON DERIVATIVES (Review)

In the field of organic synthetic pharmaceuticals, methods for the discovery, creation, and synthesis of universal molecules with pharmacological activity are rapidly advancing worldwide. Optimal synthesis methods enable the production of analytically pure biologically active compounds with the highest possible yields and minimal waste, which helps conserve resources, time, and money. The diversity of biologically active drug groups increases the ability to meet the medical needs of the population. The search for optimal synthesis methods drives the development of new technologies and techniques, which, in turn, contributes to scientific discoveries in the fields of Medicine and Chemistry. The purpose of this review is to examine the literature on methods for obtaining biologically active derivatives of N-benzylpiperidin-4-one published in scientific journals. Research Object: Derivatives of N-benzylpiperidin-4-one. Research results: The study of the reactivity of Nbenzylpiperidin-4-one derivatives confirms their versatility in various chemical reactions, highlighting their utility as chemical compounds. The results compiled in scientific literature demonstrate the potential of N-benzylpiperidin-4-one derivatives in the development of new drugs with various pharmacological properties. Conclusion: The properties of the N-benzylpiperidin-4-one molecule as a universal chemical building block indicate its wide application in medicine and pharmacology, enhancing its significance in further scientific research and the synthesis of new compounds.

Surface Chemistry Regulation in Cu4I4-Triazolate Metal-Organic Frameworks for One-Step C3H6 Purification from Quaternary C3 Mixtures.

C3H6 is a crucial building block for many chemicals, yet separating it from other C3 hydrocarbons presents a significant challenge. Herein, we report a hydrolytically stable Cu4I4-triazolate metal-organic framework (MOF) (JNU-9-CH3) featuring 1D channels decorated with readily accessible iodine and nitrogen atoms from Cu4I4 clusters and triazolate linkers, respectively. The exposed iodine and nitrogen atoms allow for cooperative binding of C3 hydrocarbons, as evidenced by in situ single-crystal crystallography and Raman spectroscopy studies. As a result, JNU-9-CH3 exhibits substantially stronger binding affinity for C3H4, CH2═C═CH2, and C3H8 than that for C3H6. Breakthrough experiments confirm its ability to directly separate C3H6 (≥99.99%) from C3H4/CH2═C═CH2/C3H8/C3H6 mixtures at varying ratios and flow rates. Overall, we illustrate the cooperative binding of C3 hydrocarbons in a Cu4I4-triazolate MOF and its highly efficient C3H6 purification from quaternary C3 mixtures. The study highlights the potential of MOF adsorbents with metal-iodide clusters for cooperative bindings and hydrocarbon separations.

Valorization of levulinic acid by esterification with 1-octanol using a novel biocatalyst derived from Araujia sericifera

Levulinic acid, which can be obtained from biomass, has sparked great interest as a biologically-based chemical building block with wide versatility and potential. Its esterification with alcohols of different chain lengths is a promising valorization process for obtaining esters with various applications in the areas of biofuels/biolubricants, food and cosmetics, among others. In this work, the enzymatic esterification of levulinic acid and 1-octanol using a biocatalyst derived from Araujia sericifera latex was studied in systems with and without solvent. The influence of the molar ratio between alcohol and acid (ranging from 2:1–1:9), the biocatalyst loading (between 7.5 % and 17.5 % relative to the acid), the volume of n-heptane used as reaction solvent (from 0 to 4 ml), and the reaction time (6 hours) were investigated. The activity and stability of the biocatalyst in successive uses were also analyzed. A conversion of 49 % was achieved when the reaction was carried out in a solvent-free system, using an alcohol/acid molar ratio of 1:7 and after 5 h of reaction. On the other hand, the conversion was 65.1 % when the reaction was conducted in a system containing 1 ml of n-heptane as solvent, an alcohol/acid molar ratio of 1:8, and 5 h of reaction. In both cases, a temperature as low as 30 °C and an agitation speed of 300 RPM were used.

The importance of both catalyst and process design in unlocking sustainable carbon feedstocks through syngas

As part of its move towards net zero, the chemical industry, over time, will transition away from fossil-based chemical feedstocks towards more sustainable, ‘green’ carbon—biomass, recycled waste and captured carbon dioxide. One gateway to transforming these feedstocks into the vital chemicals and fuels society relies on is via synthesis gas or ‘syngas’—a gaseous mixture of chemical building blocks (H 2 , CO and CO 2 ). While today the majority of syngas is produced via steam reforming of natural gas, commercially available technologies are enabling syngas production and transformation from sustainable feedstocks. The optimization of sustainable syngas technologies would not be possible without the integrated development of both catalyst and process technology and the associated skills in chemistry and chemical engineering. This paper covers three example technologies that are unlocking the role of syngas as a gateway to sustainable fuels and chemicals and highlights the innovative developments in catalyst and process design that have enabled their optimization and commercialization. This article is part of the discussion meeting issue ‘Green carbon for the chemical industry of the future’.

Biobased Chemicals from d-Galactose: An Efficient Route to 5-Hydroxymethylfurfural Using a Water/MIBK System in Combination with an HCl/AlCl3 Catalyst.

5-Hydroxymethylfurfural (HMF) is an attractive building block for biobased chemicals. Typically, ketoses like d-fructose (FRC) are suitable starting materials and give good yields of HMF in a simple aqueous phase process with a Bro̷nsted acid catalyst. With aldoses, such as d-glucose (GLU), much lower yields were reported in the literature. Here, we report an experimental and modeling study on the use of d-galactose (GAL) for HMF synthesis, using a liquid-liquid system (water/MIBK) in combination with an HCl/AlCl3 catalyst. Experiments were conducted in a batch system with temperatures between 112 and 153 °C, HCl and AlCl3 concentrations ranging from 0.02 to 0.04 M, and initial GAL concentrations between 0.1 and 1.0 M. The highest HMF yield was 49 mol % obtained for a batch time of 90 min at 135 °C. This value is much higher than in experiments with GAL in a monophasic aqueous system with HCl as the catalyst (2 mol % HMF yield) under similar reaction conditions. Based on detailed product analyses, a reaction scheme is proposed in which the isomerization of GAL to tagatose (TAG), catalyzed by the Lewis acid AlCl3, is the first and key step. TAG is then converted to HMF by Bro̷nsted acid HCl. The experimental data were modeled using a statistical approach as well as a kinetic approach. The kinetic model demonstrates a good agreement between the experimental and modeled data. Our findings reveal that temperature is the reaction variable with the most significant influence on the HMF yield. The use of a biphasic system appears to be a promising method for HMF production from GAL.

Investigation of sustainable operation oriented- economic, process and environment based multi-criteria optimization of large scale methanol production plant

Methanol is one of the main raw materials and a building block for many essential chemicals in the industry, and it is widely produced from the synthesis gas. It is used as a fuel, solvent, inhibitor, antifreeze agent, and in producing a variety of chemicals including olefins and paraffin. The global demand for methanol is 70 million tons per year and it is estimated to grow by a factor of 6–8% per year so it is necessary to develop a methanol production process, which is economical, and environment friendly. The multi-objective optimization (MOO) approach is used to optimize the large scale Lurgi two-step methanol synthesis process using the non-dominated sorting genetic algorithm-II (NSGA-II) to find the Pareto front solutions involving the process, economic, and environmental-based objectives. Methanol production rate, total energy consumption, total annual CO2 emissions, and profit are considered as objectives. The five decision variables include syngas molar flow, reactor feed pressure, reactor 1 temperature, reactor 2 temperature, and by-product mass flow in the methanol distillation column. Two constraints are set on ethanol mole fraction in the methanol stream, and methanol mole flow in water to the treatment stream. Three optimization cases (two bi-objective and one tri-objective) are developed. In the Case 1 study, CO2 emissions decreased by 65.83%, the methanol production rate increased by 10.11%, and total energy was reduced by 57.55%. The Pareto ranking is carried out using the Preference Ranking On the Basis of Ideal-average Distance (PROBID) method and the best optimal solution is reported for all cases.

Efficient synthesis of lactic acid from cellulose through the synergistic effect of zinc chloride hydrate and metal salts

The chemocatalystic conversion of cellulose, the main component of lignocellulosic biomass, to building-block chemicals in water under mild conditions, is an ideal but highly challenging process due to the robust crystal structure of cellulose. It is also the key to establishing a sustainable biomass-based chemical process. Here, we present a highly efficient and selective chemocatalytic hydrolysis of cellulose using ZnCl2·3H2O hydrate as the pretreatment reagent and water-compatible metal salts - ErCl3 as the catalyst, into lactic acid (LA), which is an important chemical building-block widely utilized in the food industry and in the production of chemicals and biodegradable plastic. With 94.0 % conversion of cellulose, an impressive LA yield of 84.6 % was achieved at 170 °C after 4 h under ambient air pressure in water. High yields of LA were also obtained from other carbohydrates, such as fructose (68.3 %), glucose (52.7 %), starch (54.4 %), and inulin (67 %). A series of experiments demonstrated that Er(III) combination with water catalyzed cascading steps of soluble cellulose into LA after ZnCl2·3H2O hydrate disrupted the hydrogen bonds in the cellulose, Zn(II) played an indirect role by promoting LA formation through inhibition of side reactions. A plausible mechanism was proposed for the chemocatalytic conversion of cellulose to LA.

Crystallization kinetics as a tool to fine-tune the catalytic activity of Na-LTA zeolite precursors in the transesterification of glycerol to glycerol carbonate

Glycerol carbonate is a versatile molecule used as a fuel additive and a chemical building block. It is a prominent route for glycerol valorization, improving the biodiesel production chain. This base-catalyzed reaction can be carried out using sodium-type zeolites if accessibility to the basic sites is ensured. Herein, we report a facile strategy to fine-tune the number and access to basic sites of Na-LTA zeolite precursors via monitoring the crystallization kinetics of the microporous material. It is demonstrated that an optimal glycerol to glycerol carbonate conversion is obtained when using the solid obtained at the beginning of the crystallization (90 min at 100 °C of hydrothermal step). Textural and spectroscopy characterization reveals that semicrystalline material presents many basic aluminate anions in a very open structure, allowing facile access to glycerol and propylene carbonate. Moreover, it is shown that this catalyst is stable in four successive reaction cycles and active in different reactions conditions

Defect Engineering of WO3 by Rapid Flame Reduction for Efficient Photoelectrochemical Conversion of Methane into Liquid Oxygenates

Photoelectrochemical (PEC) conversion is a promising way to utilize methane (CH4) as a chemical building block without harsh conditions. However, PEC CH4 conversion to value-added chemicals remains challenging due to the thermodynamically favorable over-oxidation of CH4. Here, we report WO3 nanotubes (NTs) photoelectrocatalysts for PEC CH4 conversion with high liquid product selectivity through defect engineering. By tuning the flame reduction treatment, the oxygen vacancies of WO3 NTs were carefully controlled. The optimally reduced WO3 NTs suppressed over-oxidation of CH4 showing high total C1 liquid selectivity of 69.4% and production rate of 0.174 μmol⋅cm-2⋅h-1. Scanning electrochemical microscopy revealed that oxygen vacancies can restrain the production of hydroxyl radicals, which in excess could further oxidize C1 intermediates to CO2. Additionally, band diagram analysis and computational studies elucidated that oxygen vacancies thermodynamically suppress over-oxidation. This work introduces a strategy to understand and control the selectivity of photoelectrocatalysts for direct CH4 conversion to liquids.

Kinetic Resolution as a General Approach to Enantioenrichment in Prebiotic Chemistry.

ConspectusThe origin of the single chirality of the chemical building blocks of life remains an intriguing topic of research, even after decades of experimental and theoretical work proposing processes that may break symmetry and induce chiral amplification, a term that may be defined as the enhancement of enantiomeric excess starting from prochiral substrates or from a racemic mixture or a small imbalance between enantiomers. Studies aimed at understanding prebiotically plausible pathways to these molecules have often neglected the issue of chirality, with a focus on the stereochemical direction of these reactions generally being pursued after reaction discovery. Our work has explored how the stereochemical outcome for the synthesis of amino acids and sugars might be guided to rationalize the origin of biological homochirality. The mechanistic interconnection between enantioenrichment in these two groups of molecules provides insights concerning the handedness extant in modern biology. In five separate examples involving the synthesis of life's building blocks, including sugars, RNA precursors, amino acids, and peptides, kinetic resolution emerges as a key protocol for enantioenrichment from racemic molecules directed by chiral source molecules. Several of these examples involve means not only for chiral amplification but also symmetry breaking and chirality transfer across a range of racemic monomer molecules. Several important implications emerge from these studies: one, kinetic resolution of the primordial chiral sugar, glyceraldehyde, plays a key role in a number of different prebiotically plausible reactions; two, the emergence of homochirality in sugars and amino acids is inherently intertwined, with clear synergy between the biological hand of each molecule class; three, the origin story for the homochirality of enzymes and modern metabolism points toward kinetic resolution of racemic amino acids in networks that later evolved to include sophisticated and complete catalytic and co-catalytic cycles; four, a preference for heterochiral ligation forming product molecules that cannot lead to biologically competent polymers can in fact be a driving force for a route to homochiral polymer chains; and five, enantioenrichment in complex mixtures need not be addressed one compound at a time, because kinetic resolution induces symmetry breaking and chirality transfer that may lead to general protocols rather than specific cases tailored to each individual molecule. Such chirality transfer mechanisms perhaps presage strategies utilized in modern biology.Our latest work extends the study of monomer enantioenrichment to the ligation of these molecules into the extended homochiral chains leading to the complex polymers of modern biology. A central theme in all of these reactions is the key role that kinetic resolution of a racemic mixture of amino acids or sugars plays in enabling enantioenrichment under prebiotically plausible conditions. This work has uncovered important trends in symmetry breaking, chirality transfer, and chiral amplification. Kinetic resolution of racemic mixtures emerges as a general solution for chiral amplification in prebiotic chemistry, leading to the single chirality of complex biological molecules and genetic polymers.

Emergence of Multiphase Condensates from a Limited Set of Chemical Building Blocks.

Biomolecules composed of a limited set of chemical building blocks can colocalize into distinct, spatially segregated compartments known as biomolecular condensates. While many condensates are known to form spontaneously via phase separation, it has been unclear how immiscible condensates with precisely controlled molecular compositions assemble from a small number of chemical building blocks. We address this question by establishing a connection between the specificity of biomolecular interactions and the thermodynamic stability of coexisting condensates. By computing the minimum interaction specificity required to assemble condensates with target molecular compositions, we show how to design heteropolymer mixtures that produce compositionally complex condensates by using only a small number of monomer types. Our results provide insight into how compositional specificity arises in naturally occurring multicomponent condensates and demonstrate a rational algorithm for engineering complex artificial condensates from simple chemical building blocks.