COSMOtherm is an advanced software tool for calculating the thermophysical properties of chemical compounds. This program surpasses all other similar software products in its ability to boost productivity: COSMOtherm is uniquely able to handle novel and complex compounds with unusual functional groups. Additionally, it can predict chemical properties and attributes other programs cannot.
Unlike programs which use group contribution or other fragment prediction methods and are limited to chemical structures for which empirical data exists, COSMOtherm is based on Electron Density Functional Theory (DFT) which is applicable to a much wider variety of chemical compounds. By a unique combination of DFT with continuum solvation theory and statistical thermodynamics, COSMOtherm extends the broad applicability of DFT to thermophysical property prediction. Almost any organic or inorganic compound containing H, C, N, O, Si, P, S, F, Cl, Br and I can be treated; with some restrictions other elements can be added as required.
COSMOtherm is a breakthrough product developed and updated by COSMOlogic. A database of 2500 chemical structures called COSMObase serve as a source of input into COSMOtherm. New molecules of interest can be added by the user or by COSMOlogic under a nondisclosure consultancy agreement. Additionally, a high throughput tool called COSMOfrag has been developed for drug design applications which involve the screening of tens of thousands of large molecules for desirable properties, including important drug partitioning properties.
With its new Graphical User Interface, COSMOtherm provides instant access to data essential for developing new products, improving chemical processes and solving environmental regulatory problems. The program runs on all Windows operating systems starting with Windows 98 and on all versions of Linux.
Thanks to COSMOlogic's innovative methodology, the resources and time usually required to design and develop chemical products and processes can be reduced substantially and many engineering tasks that are critical in the chemical industry can be streamlined. Examples are:
(I) Separation Processes COSMOtherm can facilitate the development of separation processes such as distillation, solvent extraction and crystallization which absorb a large part of the cost of preparing a commercial product for market.
Distillation. In other engineering programs that are used for identifying azeotropes and pinch points by performing flash calculations, the user must choose from a variety of thermodynamic models which miss some more complex azeotropes. In COSMOtherm the expertise is built in and much trial-and-error is avoided. Furthermore, in complex distillation processes there is often a critical need to find suitable entrainers which can break an azeotrope. In combination with COSMObase, COSMOtherm is very useful for screening entrainers as it can predict the efficiency of such compounds. Highly innovative entrainers have been found in this way and some are already used in running processes.
Liquid-Liquid Extraction. Many separation and purification processes depend upon the ability of a solvent to extract compounds from other solvents. COSMOtherm is the only program currently available that does not rely on group contribution methods to predict a compound's solubility in different solvents as well as in different solvent mixtures. Therefore, COSMOtherm can predict solubility for a wider range of compounds, including those which are important in the specialty chemicals, pharmaceuticals and polymer industries. As a result, the time and resources needed to conduct laboratory experiments can be greatly reduced. Experimental work can also be reduced by a magnitude when COSMOtherm is used to fine-tune solvent selectivity in processes that require selective extraction by using mixtures. This applies as well to the purification of gases by solvent extraction.
Vapor-Liquid Extraction. Since COSMOtherm can predict selective solubilities, it can be a valuable tool for identifying suitable entrainers. It is therefore useful in the many cases where gas streams from a reactor contain significant fractions of low-boiling liquids.
Crystallization. The advantages which pertain to extraction also apply to crystallization, especially when crystallization is part of the purification process. Most crystallization processes depend on the temperature-dependent solubility of the compound to be crystallized. This parameter and the relative solubility of the solute are more important for solvent selection than are the solubility or even the relative solubility of the compound. The advantage of COSMOtherm's ability to predict the temperature-dependence of solubility makes it feasible, for the first time, to make a rational choice of solvents for a much broader set of molecular structures than can be achieved by using group contribution methods. This capability also facilitates the development of anti-solvents for use in separative crystallization processes.
(II) Chemical Reactions and Catalysis. While COSMOtherm cannot estimate reaction rates a priori, it can compute may properties useful to reaction engineering. These include the estimation of activity coefficients and adsorption on catalytic surfaces. COSMOtherm can be of valuable assistance in the development of catalysts because of its ability to estimate adsorption equilibria involving the surfaces of different reactants as well as intermediates, even in complex mixtures. COSMOtherm can estimate the impact of different solvents on the reaction rate. Most other programs that perform equilibrium calculations are limited to compounds for which the heat of formation and the free energy of formation are known. COSMOtherm can estimate these properties. This capability is especially useful when complex, high molecular weight compounds are studied. Furthermore, COSMOtherm can help predict the impact of solvents on reactions by estimating the impact of a solvent on the equilibrium constant and the reaction rate. But, it should be noted that reaction applications usually require a certain level of quantum chemical expertise and hence should be done in collaboration with in-house experts or with the assistance of COSMOlogic. COSMOtherm is also useful for studying reaction mechanisms because it can estimate the thermodynamic properties of potential unstable intermediates and free radicals. This capability gives COSMOtherm a decisive advantage over other available programs used for computing the reaction equilibrium and permissible reaction pathways in complex mixtures. It may also be very useful for testing potential reaction mechanisms for proposed catalytic reactions.
(III) Polymers. COSMOtherm can provide vital information for the development of polymer products. At present, this capability is limited to nonglassy polymers that can be treated as high viscosity liquids and to block co-polymers. COSMOtherm can predict the solubility of gases, plasticizers and other additives in polymers. Since the permeability of polymer films depends on the solubility of a fluid compound in the polymer, this capability has many industrial applications. Similarly, the solubility in a given polymer of a compound to be separated (gas or liquid solute) is a critical factor in the development of selective membranes. Of special importance to development projects is COSMOtherm's ability to predict how changes in a functional group can modify solubility and selectivity. Although at present COSMOtherm does not predict polymer miscibility quantitatively, it can provide directional predictions of the effect of functional groups on the solubility and miscibility of a polymer.
(IV) Environmental Engineering. In addition to its applicability to the improvement of purification processes for the development of new compounds and drugs, COSMOtherm is an invaluable aid in the search for more environmentally friendly solvents. Since the replacement is likely to be a solvent mixture, COSMOtherm allows a wider range of potential candidates to be considered than is possible by other methods and even "green solvents" such as ionic liquids can be treated. COSMOtherm is able to predict the solubility of almost any organic in almost any solvent. This program can also be used to develop processes that are more effective for removing potential pollutants from effluents. Additionally, COSMOtherm's ability to predict very low vapor pressures as a function of operating conditions can help prevent the escape of pollutants. COSMOtherm can also predict solubilities as low as ppb for organic compounds in water. This capability is important for identifying pollutants that are likely to enter the ground water. Another COSMOtherm capability is the estimation of the adsorption of organic pollutants in a wide range of soils; variations in the organic content of soils can be measured by a single constant. At present, research is underway to extend this capability to natural zeolites and to soils in which adsorption in influenced by the inorganic crystalline structure of the soil. Of great importance in environmental engineering is COSMOtherm's ability to predict the solubility of almost any organic compound in water including all kinds of partition coefficients such as octanol/water. Since COSMOtherm does not use group contribution methods, it can handle a wider range of solvents than other programs. COSMOtherm can also be used to estimate or cross-check the values of vapor pressures, Henry's Law Constants and aqueous solubilities which are required for regulatory compliance. Although calculated values have little chance of being accepted by authorities at present, it is often helpful to know properties in advance, even if only by "orders of magnitude" estimations. This is especially true when vapor pressures or solubilities are extremely low and measurements are expensive and time-consuming. The persistence and transport of pollutants in the environment is critical for judging their impact. COSMOlogic offers a separate tool (MOOH) to predict persistance in the atmosphere which is limited by OH- radical reactivity.
(V) Drug Development. Among COSMOtherm's validated applications for drug research are water solubility, solubility in other solvents, solvent screening and, partition coefficients between different solvents including special partition properties such as log P (octanol/water), logBB and intestinal absorption. Another important capability includes the estimation of the interaction energy between a compound of interest and other molecules, e.g., hydrogen bonding, electrostatic misfit and surface charge density. The ability of COSMOtherm to calculate these physical properties and provide other valuable information for new biologically active substances makes it a powerful tool for drug discovery. Based on experience, research or modeling, the researcher who is searching for new drugs normally has specific types of chemical compositions and structures of interest in mind. The capability of COSMOtherm to estimate all the properties referred to above for any organic compound whose structure is known - before it has been synthesized - can save a great deal of expense and effort in searching for new drugs. While COSMOtherm cannot estimate the pharmaceutical activity of any given drug, some of the parameters it provides are useful indicators and others, e.g., water solubility and partition coefficients have to be within bounds for a drug to be useful. These can be strong constraints which a proposed structure may not meet. In this event, COSMOtherm can help determine if a small structural modification would alleviate the constraint without impairing the desired functional groups.
The COSMOtherm database (COSMObase) can be searched for compounds that are similar in structure which have the desired properties. However, COSMObase is limited to 2500 compounds. While a few new compounds may merit accurate estimations, it would be too time consuming to achieve this objective for a large set of similar structures as each new compound requires over twelve hours of processing before it can be added to COSMObase. The COSMOfrag extension, an auxiliary program to COSMOtherm, addresses the special need of the pharmaceutical industry to recognize trends by evaluating the effect of small structural changes on the final properties a compound. With a database of approximately 30,000 drug-like compounds, COSMOfrag can perform almost all COSMOtherm predictions for an almost limitless number of drug candidates. These advantages are achieved at the expense of accuracy, but, the results are usually sufficiently acceptable for screening purposes. Once one has identified compounds with desirable structures and properties, COSMOtherm can provide a more accurate estimation for the most promising candidates. This technique can also be applied to large-scale drug similarity searches by comparing the sigma-profiles of targets and candidates to provide key information about pharmaceutical and physiological interactions.
COSMOfrag can provide an estimate for almost any compound that can be put together from an arbitrary combination of structures because it contains such a large number of substructures. This allows for the efficient screening of thousands of compounds of a specific type. Again, the results for any specific compound can be checked and refined by using COSMOtherm. A screening tool that provides good estimates without requiring experimental work gives the drug developer a big advantage in the search for new compounds that may be candidates for specific applications or for the potential improvement of proven drugs.
Because COSMOtherm can estimate solubility in various solvents and solvent mixtures as a function of temperature, it can also be applied in the development of efficient purification methods during drug production. This program can be of great value for developing better crystallization processes and for identifying selective solvents for purification as discussed in Section I above. COSMOtherm is also useful for dealing with the environmental problems of drug manufacture as explained in Section IV on environmental engineering above.
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| COSMOlogic Product | Program Description |
|---|---|
| COSMOtherm Ver 2.00 | A thermophysical property estimation program |
| COSMObase 2000 | A database of over 2500 chemical structures for COSMOtherm |
| COSMOfrag | A large molecule screening tool for drug discovery |
