以性质为基础的同时设计过程和分子的方法

In this work, property clustering techniques and group contribution methods are combined to enable simultaneous consideration of process performance requirements and molecular property constraints. Using this methodology, the process design problem is solved to identify the property targets corresponding to the desired process performance. A significant advantage of the developed methodology is that for problems that can be satisfactorily described by only three properties, the process and molecular design problems can be simultaneously solved visually on a ternary diagram, irrespective of how many molecular fragments are included in the search space. On the ternary cluster diagram, the target properties are represented as individual points if given as discrete values or as a region if given as intervals. The structure and identity of candidate components is then identified by combining or ＂mixing＂ molecular fragments until the resulting properties match the targets.     

A systematic visual approach to molecular design via property clusters and group contribution methods

In this work, a new simple yet effective, systematic method to synthesize and design molecules is presented. Visualization of the problem is achieved by employing an annex to the recently developed property clustering techniques, which allows a high-dimensional problem to be visualized in two or three dimensions. Group contribution methods are used to predict the properties of the formulated molecules. For the molecular design problem, the target properties as well as the molecular groups that make up the formulations are identified on a ternary diagram. The target properties are represented as individual points if given as discrete values or as a region if given as intervals. The formulation of the desired molecules is achieved via linear “mixing” of molecular fragments in order to match the desired performance. It should be emphasized that the focus of this paper is the visual molecular clustering approach. Although, for systems that are described by more than three properties an algebraic clustering approach has been developed.     

通过模型为基础的溶液选择来调控药品化合物的形貌

In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a product design stage and a post-design experimental verification stage is presented. The pre-design stage addresses the tormulation of the property constraint tor crystal morphology. This involves crystallization experiments aria development of property models and constraints for morphology. In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model.The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage, in the post design experimental verification stage, the morphology of the crystals （precipitated from the designed solvent） is verified through crystallization experiments followed by product characterization via scanni＇ng electron microscopy, powder X-ray diffraction imaging and Fourier transform spectra analysis.     

通过模型为基础的溶液选择来调控药品化合物的形貌

In this paper we present a strategy for tuning the crystal morphology of pharmaceutical compounds by the appropriate choice of solvent via an optimization model. A three-stage approach involving a pre-design stage, a product design stage and a post-design experimental verification stage is presented. The pre-design stage addresses the formulation of the property constraint for crystal morphology. This involves crystallization experiments and development of property models and constraints for morphology. In the design stage various property requirements for the solvent along with crystal morphology are considered and the product design problem is formulated as a mixed integer nonlinear programming model. The design stage provides an optimal solvent/list of candidate solvents. Similar to the pre-design stage, in the post design experimental verification stage, the morphology of the crystals (precipitated from the designed solvent) is verified through crystallization experiments followed by productcharacterization via scanning electron microscopy, powder X-ray diffraction imaging and Fourier transform spectra analysis.     

A novel fluorinated polymeric product for photoreversibly switchable hydrophobic surface

A new chemical product, that is, photoreversibly switchable hydrophobic surface coating, was synthesized by atom transfer radical polymerization and graft‐from method based on molecular design. Focusing on the strategy of new product development from the chemical product engineering perspective, the product characterization, switching mechanism analysis, performance evaluation, and model interpretation were carried out to confirm the new product manufacture and to ensure the product application with a following aging test. The results show that the product enables surfaces to have reversibly switchable wettability and excellent stability after a month‐long test with eight irradiation cycles. Additionally, the wetting behavior of silicon surface can be tuned between hydrophilicity and hydrophobicity based on blank sample using the surface engineering technique (decorated with functional film and surface roughening). The product presented here can be utilized for constructing a hydrophobic surface with photo‐induced controllable wettability in moisture‐resistance, and it also offers a new technique for the manipulation of liquids in microfluidic devices. © 2014 American Institute of Chemical Engineers AIChE J 60: 4211–4221, 2014     

Design of extractive distillation for the separation of close-boiling mixtures: Solvent selection and column optimization

A practical methodology for the design and optimization of extractive distillation is proposed in this work. The extractive distillation is generally applied to the separation of close-boiling mixtures, which by conventional distillation is difficult to separate. The design and optimization of extractive distillation is more complex than that of the conventional distillation when considering the selection of suitable solvent to enhance the separation. Currently, the solvent selection can be effectively handled by the assistance of the computer-aided molecular design (CAMD) approach. The selection result may however be inconclusive due to the lack of accurate or missing parameters in the property model. In this work, the experimental verification and the property parameter determination were proved to be necessary as an additional step to achieve a successful and reliable design. The overall design methodology was illustrated through an industrial separation of C8-Aromatics mixture.     

Molecular weight determinations on polymers by electron microscopy

A technique has been developed by which molecular weight averages and distributions may be obtained for polymer fractions of high molecular weight. For glassy amorphous polymers, very dilute solutions in solvent-precipitant mixtures are atomised on to a thin carbon substrate, shadowed with platinum-carbon mixture and examined in the electron microscope. A solvent is chosen which is more volatile than the precipitant, so that on the path from the atomiser system to the substrate, and on the substrate itself, preferential evaporation of the solvent takes place. Contacts between polymer segments become more favourable than polymer-solvent contacts, resulting in the progressive contraction of the molecular coils, and the deposition of single spherical self-supporting molecules, the diameters of which can be determined from the lengths of the shadows cast by them. Molecules of polymers having glass transition temperatures below room temperature, or even slightly above, show varying degrees of collapse when prepared at room temperature. A device has been constructed which allows such polymer molecules to be deposited and shadowed at temperatures down to ?100°, at which temperature molecular collapse is not apparent. Molecular diameters may then be measured as for glassy polymers. An atomiser-separator system was constructed, which produced small droplets containing, essentially, one or zero polymer molecules, when a fraction of high molecular weight was used. All the solvent was evaporated from the droplets on the path to the cooled substrate, allowing the deposition of solvent-free molecules. Molecular weight averages and distributions are presented for a series of high-molecular-weight polymer fractions, in the glass transition temperature range from 100° to —73°. The high precision of the results from this technique is demonstrated, together with the close agreement between molecular weight averages obtained by electron microscopy, and those obtained by light-scattering and viscometry.     

FlexNovo: structure-based searching in large fragment spaces

We present a new molecular design program, FlexNovo, for structure-based searching within large fragment spaces following a sequential growth strategy. The fragment spaces consist of several thousands of chemical fragments and a corresponding set of rules that specify how the fragments can be connected. FlexNovo is based on the FlexX molecular docking software and makes use of its incremental construction algorithm and the underlying chemical models. Interaction energies are calculated by using standard scoring functions. Several placement geometry, physicochemical property (drug-likeness), and diversity filter criteria are directly integrated into the "build-up" process. FlexNovo has been used to design potential inhibitors for four targets of pharmaceutical interest (dihydrofolate reductase, cyclin-dependant kinase 2, cyclooxygenase-2, and the estrogen receptor). We have carried out calculations using different diversity parameters for each of these targets and generated solution sets containing up to 50 molecules. The compounds obtained show that FlexNovo is able to generate a diverse set of reasonable molecules with drug-like properties. The results, including an automated similarity analysis with the Feature Tree program, indicate that FlexNovo often reproduces structural motifs as well as the corresponding binding modes seen in known active structures.     

基于分子表面电荷密度分布与机器学习的混合物设计方法研究

由于混合物性能的可调控性,当前市场对其关注与日俱增。对于这类产品,基于模型的设计方法由于具有高效性以及普适性,相较于其他产品设计方法得到了更快的发展。但是对于很多性质,如气味、颜色等,准确且普适的模型尚不可得。因此,本文提出了一种基于分子表面电荷密度分布描述符（S描述符）和机器学习模型的混合物设计方法,采用描述符表征产品、再通过机器学习模型将其与性质关联,直接用于混合物产品设计。具体地,根据给定的产品性质需求,机器学习模型直接预测/设计混合物产品的S描述符;然后以欧几里德距离为指标,在给定的数据库中筛选出S描述符满足要求的候选混合物组成。最后,对候选混合物及其组分性质进行实验验证,完成设计。本文以香精的混合替代物设计作为算例,设计得到丙酸叶醇酯的两种混合香精替代物,通过实验对混合物进行了验证。结果表明,混合替代物的气味及其组分的各理化性质均与丙酸叶醇酯相近,证实本文所提出方法的有效性。     

Optimization‐based framework for computer‐aided molecular design

A new framework to automate, augment, and accelerate steps in computer‐aided molecular design is presented. The problem is tackled in three stages: (1) composition design, (2) structure determination, and (3) extended design. Composition identification and structure determination are decoupled to achieve computational efficiency. Using approximate group‐contribution methods in the first stage, molecular compositions that fit design targets are identified. In the second stage, isomer structures of solution compositions are determined systematically, and structure‐based property corrections are used to refine the solution pool. In the final stage, the design is extended beyond the scope of group‐contribution methods by using problem‐specific property models. At each design stage, novel optimization models and graph theoretic algorithms generate a large and diverse pool of candidates using an assortment of property models. The wide applicability and computational efficiency of the proposed methodology are illustrated through three case studies. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3686–3701, 2013     

一种简化的萃取溶剂分子设计方法

本研究提出一种新的萃取溶剂分子设计策略,首先以溶剂选择性为标准预选官能团,缩小分子设计的范围;再应用遗传算法对预选出的官能团进行组合,设计出符合要求的萃取溶剂分子。采用本设计的方法模拟计算了两个萃取溶剂设计实例,获得了令人满意的效果。     

A systematic method for color planning in product design

A quantitative approach for color planning in product design is addressed in this article. the color image that a product has is quantified by using the membership function of a fuzzy set. the color plan for designing an ice shaver is used as an example to show the procedure. the Hue and Tone System and the Color Image Scale are used to transform colors into images or images into colors. the composite operation for fuzzy sets is used to simulate a color projection technique to get the semantic equivalence of words and colors. A computer program is built to get the membership functions between the colors and image words. the membership functions are arranged by size and suggested to the designer to help make a decision on what color should be used. In this manner, the psychology of customers can easily be captured by the designer, consequently increasing the efficiency of the decision process. Though a simple product is taken as an example here, this systematic method can be used to design other more complicated products. In addition, the results can be used to investigate the color psychology.     

Product design: A pricing framework accounting for product quality and consumer awareness

A systematic framework has been developed to determine the optimal price of a completely new (or existing but improved) chemical product that is being launched (or relaunched) in the presence of a competing product. It has four elements. The first is a pricing model derived from a utility function with constant elasticity of substitution. It accounts for consumers' awareness of the product under consideration and consumer preferences. The second is a set of relationships relating the consumer preferences and the relevant sales data available to a relaunched product to the parameters of the pricing model. In the absence of sales data for a completely new product, the third element is a set of heuristics for choosing a pricing strategy and estimates of the pricing model parameters. The optimal price is finally determined in a profit maximization problem subject to the market size as well as any other constraints. This pricing framework allows simultaneous optimization of product quality and price using product specifications as design variables. It is illustrated with an example on energy drinks. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2462–2471, 2018     

A conceptual model for chemical product design

The fundamental principles of chemical product design and associated systematic tools, within a broad domain of chemical products including molecules, formulations, and devices, are still under development. In this article, we propose a simple and fundamental conceptual model that defines the chemical product design problem as the inversion of three central design functions: quality, property, and process functions. The classic iterative cycles of product design problems may be envisioned as alternating between inversion and evaluation of these three functions, or in other words alternating between synthesis and analysis of solutions. On top of the proposed basic structure of the overall design problem, we then discuss the formulation of some subproblems as optimization problems and describe some useful solution tools. Three application examples are provided, including a more detailed case of formulation of a pharmaceutical ointment. © 2014 American Institute of Chemical Engineers AIChE J, 61: 802–815, 2015     

Challenges and opportunities in computer-aided molecular design

In this paper, the significant development, current challenges and future opportunities in the field of chemical product design using computer-aided molecular design (CAMD) tools are highlighted. With the gaining of focus on the design of novel and improved chemical products, the traditional heuristic based approaches may not be effective in designing optimal products. This leads to the vast development and application of CAMD tools, which are methods that combine property prediction models with computer-assisted search in the design of various chemical products. The introduction and development of different classes of property prediction methods in the overall product design process is discussed. The exploration and application of CAMD tools in numerous single component product designs, mixture design, and later in the integrated process-product design are reviewed in this paper. Difficulties and possible future extension of CAMD are then discussed in detail. The highlighted challenges and opportunities are mainly about the needs for exploration and development of property models, suitable design scale and computational effort as well as sustainable chemical product design framework. In order to produce a chemical product in a sustainable way, the role of each level in a chemical product design enterprise hierarchy is discussed. In addition to process parameters and product quality, environment, health and safety performance are required to be considered in shaping a sustainable chemical product design framework. On top of these, recent developments and opportunities in the design of ionic liquids using molecular design techniques have been discussed.     

Transfer of a nanoparticle product between different mixers using latent variable model inversion

An experimental nanoparticle preparation process by solvent displacement in passive mixers is considered. The problem under investigation is to estimate the operating conditions in a target device (Mixer B) in order to obtain a product of assigned properties that has already been manufactured in a source device of different geometry (Mixer A). A large historical database is available for Mixer A, whereas a limited historical database is available for Mixer B. The difference in device geometries causes a different mixing performance within the devices, which is very difficult to capture using mechanistic models. The problem is further complicated by the fact that Mixer B can only be run under an experimental setup that is different from the one under which the available historical dataset was obtained. A joint‐Y projection to latent structures (JY‐PLS) model inversion approach is used to transfer the nanoparticle product from Mixer A to Mixer B. The Mixer B operating conditions estimated by the model are tested experimentally and confirm the model predictions within the experimental uncertainty. Since the inversion of the JY‐PLS model generates an infinite number of solutions that all lie in the so‐called null space, experiments are carried out to provide (to the authors' knowledge) the first experimental validation of the theoretical concept of null space. Finally, by interpreting the JY‐PLS model parameters from first principles, the understanding of the system physics is improved. © 2013 American Institute of Chemical Engineers AIChE J, 60: 123–135, 2014     

Efficient integration of optimal solvent and process design using molecular clustering

We present a molecular clustering approach for the efficient incorporation of solvent design information into process synthesis in the integrated design of solvent/process systems. The approach is to be used in conjunction with an integrated solvent/process design approach where the solvent design stage utilises multi-objective optimisation in order to identify Pareto optimal solvent candidates that are subsequently evaluated in a process synthesis stage. We propose to introduce the solvent design information into the process synthesis stage through the use of molecular clusters. The partitioning of the original Pareto optimal set of solvents leads to smaller compact groups of similar solvent molecules from which representative molecules are introduced into the process synthesis model as discrete options to determine the optimal process performance associated with the optimal solvent. We investigate two clustering strategies, serial and parallel clustering, that allow to effectively exploit the solvent-process design interactions to minimise the computational demands of the process synthesis stage. We further propose a clustering heuristic probability that can aid decision making in clustering and can significantly accelerate the search for the best integrated solvent-process systems. The presented method is illustrated with case studies in the design of solvents for liquid-liquid extraction, gas-absorption and extractive distillation systems.     

早强保坍型聚羧酸减水剂的制备与性能研究

基于分子结构设计原理,以甲基烯丙基聚氧乙烯醚(TPEG)、N-羟甲基丙烯酰胺(N-MA)为原料,加入自制含有较多羧基、羟基的功能大分子单体,采用自由基聚合方法,合成了兼有早强和保坍作用的新型聚羧酸减水剂.结果表明:最佳合成工艺条件为n(TPEG)∶n(AA)∶n(N-AM)∶n(大单体)为1∶7∶4∶3,反应温度为60℃,反应时间为4～5h,合成减水剂减水率达32％,混凝土初始坍落度220 mm;2 h坍落度160 mm;1d抗压强度比为185％;3 d抗压强度比为177％.利用红外光谱和凝胶渗透色谱表征减水剂分子结构和分子量,合成分子中含有大量羧基、酰胺基、酯基和醚基,重均分子量均在3.6万左右,数均分子量均在2万左右,分子量分布均匀.采用X射线衍射分析1d龄期水泥试样的水化产物组成,相比于空白试样,掺加减水剂能延缓硅酸盐熟料矿物的水化进程,但促进了AFt的形成,发生AFt向AFm的转变,加快水化速率,具有一定的早强作用.