Progress in the Synthesis of Colloidal Machines.

For the past decade, the field of colloidal science has expanded the collection of colloidal particles to include an entire library of subunits that can be isotropic or anisotropic in terms of structural morphology or chemical composition. Using anisotropic subunits, the field has assembled a variety of static and dynamic structures. For this Account, we use the umbrella term "dynamic colloids" to describe subunits capable of movement, shape-shifting, or any other type of action in response to a stimulus and "static colloids" to describe those that are unresponsive to such stimuli. We view dynamic colloids as an access point to colloidal machines, a unique and emerging subfield of machines, and colloidal science. The assembly of dynamic subunits into colloidal machines differs from traditional self-assembly only in the final structures assembled, not the methods used. Dynamic assemblies have the capacity to interact with their environment in ways that traditional anisotropic self-assemblies do not. Here, we present the current state of the field of colloidal science toward the introduction of the next wave of colloidal machines. Machines are ubiquitous in nature and synthetic systems, governing every aspect of life. In mechanics, a machine is a device that transmits or modifies force or motion. In biology, nature's machines such as kinesin or ATP synthetase are essential to life. In the synthetic realm, molecular machines and nanomachines, recognized with the Nobel prize, include diverse systems, such as molecular rotors and elevators fabricated using bottom-up synthetic methods. On the microscale, microscopic motors based on microelectromechanical systems (MEMs) have been achieved via top-down methods such as micromachining. On the colloidal scale, machines are conspicuously absent due, in part, to the difficulty in navigating combinatory design spaces. We view colloidal machines (100 nm to 10 µm) as the next line of miniaturization in machines. Due to the bottom-up fabrication methods generally used in creating dynamic colloids, one can achieve complexity at a smaller scale than possible with top-down approaches. The introduction of colloidal scale machines would bridge the gap between the microscopic world with its macroscopic counterparts, the nanoworld with its molecular machines, and the biological world with nature's machinery. Reported colloidal machines to date are apparatuses that consist of multiple components of a single composition of dynamic subunits that come together to perform some work. The next step toward complex colloidal machines is systems containing multiple dynamic colloidal scale components that come together to act in tandem to perform some work on the surrounding environment. We envision repurposing a library of dynamic particles originally intended to be used as anisotropic subunits into dynamic components of a colloidal machine. Computationally, the idea of colloidal machines has been extensively explored; however, synthetically, there has been limited exploration. In order to implement this existing library into colloidal machines, the key next step is the development of synthetic combinatorial design spaces.

Functionalized [2.2]Paracyclophanedienes as Monomers for Poly(p-phenylenevinylene)s.

Poly(p-phenylenevinylene)s (PPVs) featuring complex side-chains, to date, have only been synthesized by nonliving polymerization methods which have no control over PPV molecular weights, dispersities, or end groups. [2.2]Paracyclophane-1,9-diene (pCpd) has gained attention as a monomer for its ability to be ring-opened to PPV in a living fashion. pCpd, an organic cyclic scaffold with planar chirality, has seen minimal structural diversity due to the harsh reaction conditions required to afford the highly strained compound. Herein, we introduce a general method to overcome this by targeting the synthesis of a monohydroxy-pCpd via mono-demethylation of a dialkoxy-pCpd. The monohydroxy-pCpd can then be functionalized easily, which we demonstrate using three distinct side-chains with four moieties commonly incorporated in conjugated polymers: an alkyl bromide, an oligo(ethylene glycol) chain, an enantiomerically pure side-chain, and a Boc-protected amine. These monofunctionalized-pCpds were investigated as monomers in the ring-opening metathesis polymerization (ROMP) to afford functionalized PPVs in a living manner. The functional-group-containing PPVs are synthesized with full control over their end groups, repeat units, and dispersities. The feasibility of post-polymerization modifications to incorporate any desired moiety to PPV fabricated by this method was demonstrated using an azide-alkyne click reaction. All synthesized PPVs were soluble in organic solvents and display the same fluorescent emission, indicating their conjugated backbones are unaltered.

Multiscale Modeling Approach for the Aldol Addition Reaction in Multicompartment Micelle-Based Nanoreactor.

Water has emerged as a versatile solvent for organic chemistry in recent years due to its abundance, low cost, and environmental friendliness. However, one of the most important reactions, the aldol reaction, in the presence of excess water exhibits low yields and poor enantioselectivities. In this regard, we have employed a multiscale modeling approach to investigate the aldol addition reaction catalyzed by l-proline in the hydrophobic compartment of multicompartment micelle (MCM) nanoreactor consisting of amphiphilic bottlebrush copolymer, which minimizes the water content at the reactive site. Through performing dissipative particle dynamics (DPD) simulation, it is found that the "clover-like" morphology of the MCM is formed from multiblock copolymer with a sequence of ethylene oxide-based hydrophilic blocks, styrene lipophilic blocks, l-proline catalyst blocks, and a pentafluorostyrene fluorophilic block in aqueous media. We find that the vicinity of the catalyst in the clover-like MCM has a low dielectric environment, which could facilitate the aldol addition reaction. Our DFT calculations demonstrate that the asymmetric aldol addition of l-proline-catalyzed acetone and 4-nitrobenzaldehyde is energetically more favorable under the low dielectric environment in MCM compared with other commonly used solvents such as DMSO, water, and vacuum condition.

3D Printing Type 1 Bovine Collagen Scaffolds for Tissue Engineering Applications-Physicochemical Characterization and In Vitro Evaluation.

Collagen, an abundant extracellular matrix protein, has shown hemostatic, chemotactic, and cell adhesive characteristics, making it an attractive choice for the fabrication of tissue engineering scaffolds. The aim of this study was to synthesize a fibrillar colloidal gel from Type 1 bovine collagen, as well as three dimensionally (3D) print scaffolds with engineered pore architectures. 3D-printed scaffolds were also subjected to post-processing through chemical crosslinking (in N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide) and lyophilization. The scaffolds were physicochemically characterized through Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis, Differential Scanning Calorimetry, and mechanical (tensile) testing. In vitro experiments using Presto Blue and Alkaline Phosphatase assays were conducted to assess cellular viability and the scaffolds' ability to promote cellular proliferation and differentiation. Rheological analysis indicated shear thinning capabilities in the collagen gels. Crosslinked and lyophilized 3D-printed scaffolds were thermally stable at 37 °C and did not show signs of denaturation, although crosslinking resulted in poor mechanical strength. PB and ALP assays showed no signs of cytotoxicity as a result of crosslinking. Fibrillar collagen was successfully formulated into a colloidal gel for extrusion through a direct inkjet writing printer. 3D-printed scaffolds promoted cellular attachment and proliferation, making them a promising material for customized, patient-specific tissue regenerative applications.

Bent and Twisted: Synthesis of an Alkoxy-Substituted (1,5)Naphthalene-paracyclophanediene.

This contribution describes the synthesis of [2.2](1,5)naphthalenoparacyclophane-1,13-diene in four steps from 1,5-bis(bromomethyl)naphthalene and 1,4-benzenedimethanethiol. Consisting of 2,6-dioctyloxynaphthalene and benzene moieties, the effects of differing arene size on the structure, strain energy, and chemical reactivity of the cyclophanediene are examined. Despite a strain energy of 24.3 kcal/mol, the naphthalenoparacyclophanediene was unreactive toward a library of olefin metathesis catalysts. This diminished reactivity can be explained by the steric hindrance of the twisted olefin. Incorporation of an electron donor (naphthalene) into the rigid paracyclophanediene structure can allow for applications in optoelectronics, chiral ligands, and planar chiral materials.

Nonorthogonal Cascade Catalysis in Multicompartment Micelles.

Multicompartment micelles (MCMs) containing acid and base sites in discrete domains are prepared from poly(norbornene)-based amphiphilic bottlebrush copolymers in aqueous media. The acid and base sites are localized in different compartments of the micelle, enabling the nonorthogonal reaction sequence: deacetalization - Knoevenagel condensation - Michael addition of acetals to 2-amino chromene derivatives. Computational simulations using dissipative particle dynamics (DPD) elucidated the bottlebrush composition required to effectively site-isolate the nonorthogonal catalysts. This contribution presents MCMs as a new class of nanostructures for one-pot multistep nonorthogonal cascade catalysis, laying the groundwork for the isolation of three or more incompatible catalysts to synthesize value-added compounds in a single reaction vessel, in water.

Orthogonal Supramolecular Assemblies Using Side-Chain Functionalized Helical Poly(isocyanide)s.

Mimicking the structure of proteins using synthetic polymers requires building blocks with structural similarity and the use of various noncovalent and dynamic covalent interactions. We report the synthesis of helical poly(isocyanide)s bearing diaminopyridine and pyridine side-chains and the multistep functionalization of the polymers' side-chains using hydrogen bonding and metal coordination. The orthogonality of the hydrogen bonding and metal coordination was proved by varying the sequence of the multistep assembly. The two side-chain functionalizations are reversible through the use of competitive solvents and/or competing ligands. Throughout the assembly and disassembly, the helical conformation of the polymer backbone is sustained as proved by circular dichroism spectroscopy. These results open the possibility to incorporate helical domains into complex polymer architectures and create a helical scaffold for smart materials.

A Polymer Canvas with the Stiffness of the Bone Matrix to Study and Control Mesenchymal Stem Cell Response.

Reproducing in vitro the complex multiscale physical features of human tissues creates novel biomedical opportunities and fundamental understanding of cell-environment interfaces and interactions. While stiffness has been recognized as a key driver of cell behavior, systematic studies on the role of stiffness have been limited to values in the KPa-MPa range, significantly below the stiffness of bone. Here, a platform enabling the tuning of the stiffness of a biocompatible polymeric interface up to values characteristic of human bone is reported, which are in the GPa range, by using extremely thin polymer films on glass and cross-linking the films using ultraviolet (UV) light irradiation. It is shown that a higher stiffness is related to better adhesion, proliferation, and osteogenic differentiation, and that it is possible to switch on/off cell attachment and growth by solely tuning the stiffness of the interface, without any surface chemistry or topography modification. Since the stiffness is tuned directly by UV irradiation, this platform is ideal for rapid and simple fabrication of stiffness patterns and gradients, thus representing an innovative tool for combinatorial studies of the synergistic effect of tissue environmental cues on cell behavior, and creates new opportunities for next-generation biosensors, single-cell patterning, and lab-on-a-chip devices.

Customized metallodielectric colloids and their behavior in dielectrophoretic fields.

A synthetic strategy for fabricating colloidal particles with spatially segregated amine-functionalized lobes enables regioselective coating with gold to afford metallodielectric particles with a variety of shapes and lobe sizes. This approach can produce either dissymmetric dumbbell-shaped two-lobed Au-TPM particles (Au-T) or dissymmetric or symmetric three-lobed particles with gold coating on one (Au-T-T and T-Au-T) or two lobes (Au-T-Au). Dielectrophoretic (DEP) forces exerted by an AC field confined between two opposing electrodes generate aggregates ranging from 1D chains to 2D close-packed lattices, depending on the particle shape and lobe arrangement. The aggregate structures reflect the lowest energy configurations resulting from the induced dipole moments created in particle lobes within the confined electric field.

Catalytically Active Multicompartment Micelles.

This article presents the self-assembly behavior of multicompartment micelles (MCMs) in water into morphologies with multiple segregated domains and their use as supports for aqueous catalysis. A library of poly(norbornene)-based amphiphilic bottlebrush copolymers containing covalently attached l-proline in the hydrophobic, styrene, and pentafluorostyrene domains and a poly(ethylene glycol)-containing repeat unit as the hydrophilic block have been synthesized using ring-opening metathesis polymerization. Interaction parameter (χ) values between amphiphilic blocks were determined using a Flory-Huggins-based computational model. The morphologies of the MCMs are observed via cryogenic transmission electron microscopy and modeled using dissipative particle dynamic simulations. The catalytic activities of these MCM nanoreactors were systematically investigated using the aldol addition between 4-nitrobenzaldehyde and cyclohexanone in water as a model reaction. MCMs present an ideal environment for catalysis by providing control over water content and enhancing interactions between the catalytic sites and the aldehyde substrate, thereby forming the aldol product in high yields and selectivities that is otherwise not possible under aqueous conditions. Catalyst location, block ratio, and functionality have substantial influences on micelle morphology and, ultimately, catalytic efficiency. "Clover-like" and "core-shell" micelle morphologies displayed the best catalytic activity. Our MCM-based catalytic system expands the application of these nanostructures beyond selective storage of guest molecules and demonstrates the importance of micelle morphology on catalytic activity.

Synthesis and Polymerization of an ortho-para-Substituted Tetraalkoxy [2.2]Paracyclophane-1,9-diene.

This contribution describes the synthesis of an unsymmetrical substituted tetraalkoxy[2.2]paracyclophane-1,9-diene comprised of an ortho-substituted and a para-substituted dioctyloxybenzene. (Sp)-4,5,12,15-tetraoctyloxy-[2.2]paracyclophane-1,9-diene ((Sp)-pCpd) and (Rp)-4,5,13,16-tetraoctyloxy-[2.2]paracyclophane-1,9-diene ((Rp)-pCpd) are formed as planar chiral enantiomers. Unlike other tetraalkoxy-substituted pCpds that form as diastereomers, both the (Sp)-pCpd and the (Rp)-pCpd can be polymerized via ring-opening metathesis polymerization (ROMP) using Grubbs' third generation initiator (G3) as it is achiral. Living ROMP afford copolymers featuring alternating cis,trans-poly(p-phenylenevinylene)s (PPV)s. The polymers' unique, blue-shifted optical properties are due to the alkoxy-substitution in the polymer's backbone and the resulting materials could be photoisomerized to the all-trans polymer. This strategy affords tetraalkoxy-pCpd monomers in high yields for the polymerization of soluble PPVs with low or narrow dispersities.

Supramolecular Helical Miktoarm Star Polymers.

We report a hydrogen-bonded supramolecular miktoarm star polymer containing three distinct helical arms. Our design involves two helical poly(methacrylamide) arms connected by a barbituric acid (Ba) at the center, prepared through the reversible addition-fragmentation chain-transfer polymerization with a bifunctional agent. Together with a telechelic helical poly(isocyanide) end-functionalized with a Hamilton Wedge (HW) that is complementary to Ba, the two components assemble into an AB2-type star copolymer. The assembly is driven by the hydrogen bonding between HW and Ba, which is quantified by 1H NMR titration and isothermal titration calorimetry. Gel-permeation chromatography provides evidence for the formation of the desired miktoarm star architecture. This strategy of site-specific functionalization on helical polymers provides a modular approach to preparing nonlinear supramolecular ensembles with topologically diverse building blocks.

Photoresponsive Azobenzene-Functionalized Shell Cross-Linked Micelles for Selective Asymmetric Transfer Hydrogenation.

We describe the substrate-selective asymmetric transfer hydrogenation of aromatic ketones using rhodium complexes immobilized on a photoresponsive nanoreactor. The nanoreactor switches its morphology upon light irradiation in a wavelength-selective manner. Kinetic studies show that the gated behavior in the cross-linking layer is key to discriminating among substrates and reagents during catalysis. Under ultraviolet light irradiation, the nanoreactor displays substrate selectivity, converting smaller ketone substrates faster to the corresponding secondary alcohols.

Compartmentalisation of molecular catalysts for nonorthogonal tandem catalysis.

The development of nonorthogonal tandem catalysis enables the use of a combination of arbitrary catalysts to rapidly synthesize complex products in a substainable, efficient, and timely manner. The key is to compartmentalise the molecular catalysts, thereby overcoming inherent incompatibilities between individual catalysts or reaction conditions. This tutorial review analyses the development of the past two decades in the field of nonorthogonal tandem catalysis with an emphasis on compartmentalisation strategies. We highlight design principles of functional materials for compartmentalisation and suggest future directions in the field of nonorthogonal tandem catalysis.

Near-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostics.

This contribution describes the design and synthesis of multifunctional micelles based on amphiphilic brush block copolymers (BBCPs) for imaging and selective drug delivery of natural anticancer compounds. Well-defined BBCPs were synthesized via one-pot multi-step sequential grafting-through ring-opening metathesis polymerization (ROMP) of norbornene-based macroinitiators. The norbornenes employed contain a poly(ethylene glycol) methyl ether chain, an alkyl bromide chain, and/or a near-infrared (NIR) fluorescent cyanine dye. After block copolymerization, post-polymerization transformations using bromide-azide substitution, followed by the strain-promoted azide-alkyne cycloaddition (SPAAC) allowed for the functionalization of the BBCPs with the piplartine (PPT) moiety, a natural product with well-documented cytotoxicity against cancer cell lines, via an ester linker between the drug and the polymer side chain. The amphiphilic BBCPs self-assembled in aqueous media into nano-sized spherical micelles with neutral surface charges, as confirmed by dynamic light scattering analysis and transmission electron microscopy. During self-assembly, paclitaxel (PTX) could be effectively encapsulated into the hydrophobic core to form stable PTX-loaded micelles with high loading capacities and encapsulation efficiencies. The NIR fluorescent dye-containing micelles exhibited remarkable photophysical properties, excellent colloidal stability under physiological conditions, and a pH-induced disassembly under slightly acidic conditions, allowing for the release of the drug in a controlled manner. The in vitro studies demonstrated that the micelles without the drug (blank micelles) are biocompatible at concentrations of up to 1 mg mL-1 and present a high cellular internalization capacity toward MCF-7 cancer cells. The drug-functionalized micelles showed in vitro cytotoxicity comparable to free PPT and PTX against MCF-7 and PC3 cancer cells, confirming efficient drug release into the tumor environment upon cellular internalization. Furthermore, the drug-functionalized micelles exhibited higher selectivity than the pristine drugs and preferential cellular uptake in human cancer cell lines (MCF-7 and PC3) when compared to the normal breast cell line (MCF10A). This study provides an efficient strategy for the development of versatile polymeric nanosystems for drug delivery and image-guided diagnostics. Notably, the easy functionalization of BBCP side chains via SPAAC opens up the possibility for the preparation of a library of multifunctional systems containing other drugs or functionalities, such as target groups for recognition.

Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform.

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol-ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.

Intramolecular Folding of Coil-Helix Block Copolymers Induced by Quadrupole Interactions.

True tertiary architectures with defined local secondary structures are rare in synthetic systems. Adapting well-developed synthetic building blocks and controlling their folding through diverse interactions can be a general approach toward this goal. In this contribution, the synthesis of 3D hierarchical assemblies with distinct secondary domains formed through the intramolecular folding of a block copolymer containing a coil-like poly(styrene) (PS) block with a helical poly(isocyanide) block induced by phenyl-pentafluorophenyl quadrupole interactions is reported. The PS block is prepared via atom-transfer radical polymerization and end functionalized with a nickel complex that serves as a macroinitiator for the polymerization of chiral isocyanides bearing pentafluorophenyl pendants. The folding behavior of the coil-helix block copolymers is investigated by dynamic light scattering, NMR spectroscopy, wide-angle X-ray scattering, and differential scanning calorimetry.

Secondary Structure in Nonpeptidic Supramolecular Block Copolymers.

Proteins contain a level of complexity-secondary and tertiary structures-that polymer chemists aim to imitate. The bottom-up synthesis of protein-mimicking polymers mastering sequence variability and dispersity remains challenging. Incorporating polymers with predefined secondary structures, such as helices and π-π stacking sheets, into block copolymers circumvents the issue of designing and predicting one facet of their 3D architecture. Block copolymers with well-defined secondary-structure elements formed by covalent chain extension or supramolecular self-assembly may be considered for localized tertiary structures.In this Account, we describe a strategy toward block copolymers composed of units bearing well-defined secondary structures mixed in a "plug-and-play" manner that approaches a modicum of the versatility seen in nature. Our early efforts focused on the concept of single-chain collapse to achieve folded secondary structures through either hydrogen bonding or quadrupole attractive forces. These cases, however, required high dilution. Therefore, we turned to the ring-opening metathesis polymerization (ROMP) of [2.2]paracyclophane-1,9-dienes (pCpd), which forms conjugated, fluorescent poly(p-phenylenevinylene)s (PPVs) evocative of ß-sheets. Helical building blocks arise from polymers such as poly(isocyanide)s (PICs) or poly(methacrylamide)s (PMAcs) containing bulky, chiral side groups while the coil motif can be represented by any flexible chain; we frequently chose poly(styrene) (PS) or poly(norbornene) (PNB). We installed moieties for supramolecular assembly at the chain ends of our "sheets" to combine them with complementary helical or coil-shaped polymeric building blocks.Assembling hierarchical materials tantamount to the complexity of proteins requires directional interactions with high specificity, covalent chain extension, or a combination of both chemistries. Our design is based on functionalized reversible addition-fragmentation chain-transfer (RAFT) agents that allowed for the introduction of recognition motifs at the terminus of building blocks and chain-terminating agents (CTAs) that enabled the macroinitiation of helical polymers from the chain end of ROMP-generated sheets and/or coils. To achieve triblock copolymers with a heterotelechelic helix, we relied on supramolecular assembly with helix and coil-shaped building blocks. Our most diverse structures to date comprised a middle block of PPV sheets, parallel or antiparallel, and supramolecularly or covalently linked, respectively, end-functionalized with molecular recognition units (MRUs) for orthogonal supramolecular assembly. We explored PPV sheets with multiple folds achieved by chain extension using alternating pCpd and phenyl-pentafluorophenyl ß-hairpin turns. Using single-molecule polarization spectroscopy, we showed that folding occurs preferentially in multistranded over double-stranded PPV sheets. Our strategy toward protein-mimicking and foldable polymers demonstrates an efficient route toward higher ordered, well-characterized materials by taking advantage of polymers that naturally manifest secondary structures. Our studies demonstrate the retention of distinct architectures after complex assembly, a paradigm that we believe may extend to other polymeric folding systems.

Compartmentalization and Photoregulating Pathways for Incompatible Tandem Catalysis.

This contribution describes an advanced compartmentalized micellar nanoreactor that possesses a reversible photoresponsive feature and its application toward photoregulating reaction pathways for incompatible tandem catalysis under aqueous conditions. The smart nanoreactor is based on multifunctional amphiphilic poly(2-oxazoline)s and covalently cross-linked with spiropyran upon micelle formation in water. It responds to light irradiation in a wavelength-selective manner switching its morphology as confirmed by dynamic light scattering and cryo-transition electron microscopy. The compartmental structure renders distinct nanoconfinements for two incompatible enantioselective transformations: a rhodium-diene complex-catalyzed asymmetric 1,4-addition occurs in the hydrophilic corona, while a Rh-TsDPEN-catalyzed asymmetric transfer hydrogenation proceeds in the hydrophobic core. Control experiments and kinetic studies showed that the gated behavior induced by the phototriggered reversible spiropyran to merocyanine transition in the cross-linking layer is key to discriminate among substrates/reagents during the catalysis. The smart nanoreactor realized photoregulation to direct the reaction pathway to give a multichiral product with high conversions and perfect enantioselectivities in aqueous media. Our SCM catalytic system, on a basic level, mimics the concepts of compartmentalization and responsiveness Nature uses to coordinate thousands of incompatible chemical transformations into streamlined metabolic processes.

Top-Down Heterogeneous Colloidal Engineering Using Capillary Assembly of Liquid Particles.

Capillary assembly of liquid particles (CALP) is a microfabrication strategy for engineering arbitrarily shaped polymer colloids. The method entails depositing emulsion particles into patterned microarrays within a fluidic cell: coalescence, polymerization, and extraction of the deposited material engender faceted colloids. Herein, the versatility of CALP is demonstrated by using both consecutive assembly and heterogeneous coassembly to engineer geometrically diverse Janus and patchy colloids. Liquid particles (LPs) can be patterned laterally across the plane of the template by manipulating the capillary immersion force, liquid particle hardness, and rate of coalescence. Bilayers of different polymeric LPs and patchy microarrays are fabricated, comprising solid colloids made from various materials including poly(styrene), p-styryltrimethoxysilane, and iron oxide. Eleven different structures including concentric Janus squares, triblock ellipsoids, and planar tetramer and pentagonal patchy particles are described. All particles are fluorescently labeled, resist flocculation, withstand extended heating, and endure dispersion in organic solvent. Further crystallization and processing into colloid-based microscale devices is therefore anticipated. Heterogeneous CALP combines top-down microfabrication with bottom-up synthesis to engineer nonequilibrium particle structures that cannot be made with wet chemistry. CALP enables the design and fabrication of colloids with complex internal construction to target hierarchical functional materials. Ultimately, the integration of colloidal building blocks comprising multiple components that are independently addressable is crucial for the development of nano/micromaterials such as filtration devices, sensors, diagnostics, solid-state catalysts, and optical electronics.