ALCHEM

ACS Symposium Series American Chemical Society Washington, DC, 1977. 

A linear symbolic code has been developed for this purpose. 

PRIORITY is a value representing the initial plausibility of the transform, before consideration of the reaction site context. Values range from -50 to 100. CHARACTER describes what kinds of structural modifications the transform can make, e.g., ALTERS GROUP, BREAKS RING. 

CONDITIONS are generalized classes of reaction conditions, rather than specific reagents. The advantage being that any new reagent can always be represented as belonging to a general class. These are described later in this paper. 

SCOPE and LIMITATIONS comprise the main body of the transform. They are situation-action rules which explore the context of the reaction site and alter the PRIORITY or other values to reflect the influence certain structural features have on the plausibility of this reaction. PRIORITY is one of eight vaiables 

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Silver nitrate forms colorless, rhombic crystals. It is dimorphic and changes to the hexagonal rhombohedral form at 159.8°C. It melts at 212°C to a yellowish Hquid which solidifies to a white, crystalline mass on cooling. An alchemical name, lunar caustic, is stiU appHed to this fused salt. In the presence of a trace of nitric acid, silver nitrate is stable to 350°C. It decomposes at 440°C to metallic silver, nitrogen, and nitrogen oxides. Solutions of silver nitrate are usually acidic, having a pH of 3.6—4.6. Silver nitrate is soluble in ethanol and acetone. 

Here, 7 runs over all simulations and k, I run over all bins. These equations can be solved iteratively, assuming an initial set oi fj (e.g., fj =1), then calculating p°i from Eq. (34) and updating Ihe fj by Eq. (35), and so on, until thep°i no longer vary, i.e., the two equations are self-consistent. Erom the p°i = P(qt, sp and Eq. (27), one then obtains the free energy of each bin center (q, sp. Error estimates are also obtained [46]. The method can be applied to a one-dimensional reaction coordinate or generalized to more than two dimensions and to cases in which simulations are run at several different temperatures [46]. It also applies when the reaction coordinates are alchemical coupling coordinates (see below and Ref. 47). 

Consider an alchemical transformation of a particle in water, where the particle s charge is changed from 0 to i) (e.g., neon sodium q = ). Let the transformation be performed first with the particle in a spherical water droplet of radius R (formed of explicit water molecules), and let the droplet then be transferred into bulk continuum water. From dielectric continuum theory, the transfer free energy is just the Born free energy to transfer a spherical ion of charge q and radius R into a continuum with the dielectric constant e of water ... 

The idea of a finite simulation model subsequently transferred into bulk solvent can be applied to a macromolecule, as shown in Figure 5a. The alchemical transformation is introduced with a molecular dynamics or Monte Carlo simulation for the macromolecule, which is solvated by a limited number of explicit water molecules and otherwise surrounded by vacuum. Then the finite model is transferred into a bulk solvent continuum... 

A very simple version of this approach was used in early applications. An alchemical charging calculation was done using a distance-based cutoff for electrostatic interactions, either with a finite or a periodic model. Then a cut-off correction equal to the Born free energy, Eq. (38), was added, with the spherical radius taken to be = R. This is a convenient but ill-defined approximation, because the system with a cutoff is not equivalent to a spherical charge of radius R. A more rigorous cutoff correction was derived recently that is applicable to sufficiently homogeneous systems [54] but appears to be impractical for macromolecules in solution. 

Another variant that may mrn out to be the method of choice performs the alchemical free energy simulation with a spherical model surrounded by continuum solvent, neglecting portions of the macromolecule that lie outside the spherical region. The reaction field due to the outer continuum is easily included, because the model is spherical. Additional steps are used to change the dielectric constant of that portion of the macromolecule that lies in the outer region from its usual low value to the bulk solvent value (before the alchemical simulation) and back to its usual low value (after the alchemical simulation) the free energy for these steps can be obtained from continuum electrostatics [58]. 

Finally, an alchemical free energy simulation is needed to obtain the free energy difference between any one substate of system A and any one substate of system B, e.g., Ai- In practice, one chooses two substates that resemble each other as much as possible. In the alchemical simulation, it is necessary to restrain appropriate parts of the system to remain in the chosen substate. Thus, for the present hybrid Asp/Asn molecule, the Asp side chain should be confined to the Asp substate I and the Asn side chain confined to its substate I. Flat-bottomed dihedral restraints can achieve this very conveniently [38], in such a way that the most populated configurations (near the energy minimum) are hardly perturbed by the restraints. Note that if the substates AI and BI differ substantially, the transfomnation will be difficult to perform with a single-topology approach. 

A powerful and general technique to enhance sampling is the use of umbrella potentials, discussed in Section IV. In the context of alchemical free energy simulations, for example, umbrella potentials have been used both to bias the system toward an experimentally determined conformation [26] and to promote conformational transitions by reducing dihedral and van der Waals energy terms involving atoms near a mutation site [67]. 

Nitric acid is one of the three major acids of the modem chemical industiy and has been known as a corrosive solvent for metals since alchemical times in the thirteenth centuiy. " " It is now invariably made by the catalytic oxidation of ammonia under conditions which promote the formation of NO rather than the thermodynamically more favoured products N2 or N2O (p. 423). The NO is then further oxidized to NO2 and the gases absorbed in water to yield a concentrated aqueous solution of the acid. The vast scale of production requires the optimization of all the reaction conditions and present-day operations are based on the intricate interaction of fundamental thermodynamics, modem catalyst technology, advanced reactor design, and chemical engineering aspects of process control (see Panel). Production in the USA alone now exceeds 7 million tonnes annually, of which the greater part is used to produce nitrates for fertilizers, explosives and other purposes (see Panel). 

Radioactixity. Philadelphia Chemical Heritage Foundation. Rayner-Canham, M., and Rayner-Canham, G. (1998). Women in Chemistry Their Changing Roles from Alchemical Times to the Mid-Twentieth Century. Philadelphia Chemical Heritage Foundation. 

I. Historical. PA is probably the earliest known nitrophenol. According to Urbanski (Ref 35) it is mentioned in the alchemical writings of Glauber as early as 1742. Glauber reacted nitric acid with wool or hom and isolated PA in the... 

When the new Hills extension was opened, a large mural featuring alchemical symbols and motifs radiating from a central sun was commissioned to adorn the foyer. Inspection of the golden orb revealed a beaming face bearing the unmistakable features of the department s leader. 

Some Paracelsian alchemists, especially Heinrich Khun rath (ca. 1560-1605) and Stefan Michelspacher (active ca. 1615-23), were objects of persecution on the part of hoth Lutheran and Catholic authorities. Khunrath was an alchemist from Saxony, the heartland of the Reformation, but his theological stance was characteristic of the second generation of Protestants who felt that Luther s work had been left incomplete and that another religious reform was essential. In Khunrath s ideas this would take the form of a Lutheranism that could accommodate an autonomous personal piety. To express their Lutheran piety intellectually the alchemists employed the terms of Paracelsian theosophy, while they found an emotive outlet in the mystical experience of the power and grace of the Holy Spirit. They felt themselves to be inspired (literally breathed ) by the Spirit, a force that they identified with alchemical pneuma. Khunrath called himself an enthusiast, hlled with the presence of the divine. 

One important reason for the emergence of Paracelsian alchemical illustration may have been its function as a psychological compensation for the rejection of Catholic imagery by the Protestants and the resulting spiritual and emotional insecurity experienced by many of the faithful. It is not merely coincidental that Paracelsian iconography should appear in Protestant areas where traditional Catholic icons had been destroyed. (The development of a specihcally Catholic interest in alchemy, however, was a phenomenon of the mid-seventeenth century developed in the work of Athanasius Kircher and other Jesuits.) ... 

Helena M. E. De Jong, Michael Maier s Atalanta Eugiens Sources of an Alchemical Book of Emblems (Leiden E. J. BriU, 1969). 

In a manner comparable to Christian eschatology, alchemical literature insisted on its own purificatory rituals that involved the preliminary torture, death and dismemberment of the prima materia. The canonical Catholic depiction of Christ s sacrificed body was a primary source for sixteenth and seventeenth century illustrations of the tortured body in anatomical and alchemical publications. In eflfect, the practice of Paracelsian alchemical medicine and surgery had a sacramental connotation, since the physician acted on the human body in the same manner as God worked on the great universal Macrocosmic Body. In like manner, the Paracelsian physician introduced the universal panacea, a liquid form of the philosopher s stone, into the alchemical alembic that was the Microcosmic human body. This alchemical medicine was permeated with the starry virtues of the heavens and the grace of Christ s Spirit, redeeming the body and soul of the patient by granting him not only an extended life on earth, but even eternal salvation. 

The concept of a Cosmic Man, the All, the soul of both the universe and humanity, was a significant factor in the theosophy of Paracelsus (1493-1541). The first visual depiction of this Being in the form of Christ-Anthropos, the Son of Man, appeared in Khunrath s alchemical treatise in 1595 (fig. 3). It was developed into the image of the Macrocosmic Man by Robert Fludd who was a prolihc encyclopaedist of Hermetic, medical and mechanical knowledge. In his Philosophia Sacra (1626), Fludd recalled texts in the Hermetic corpus (ca. second century AD) which recounted how Man ( Anthropos ), the divine Son of God, had created the world by uniting with Nature ( Physis ). ... 

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