The Structure Hypothesis

The molecular concept has become so central in chemistry that understanding of chemical events is commonly assumed to consist of relating experimental observations to micro events at the molecular level, which means changes in molecular structure. In this sense molecular structure is a fundamental theoretical concept in chemistry. As the micro changes are invariably triggered by electron transfer, the correct theory at the molecular level must be quantum mechanics. It is therefore surprising that a quantum theory of molecular structure has never developed. This failure stems from the fact that physics and chemistry operate at different levels and that grafting the models of physics onto chemistry produces an incomplete picture. 

Although the physics model may give a reasonable qualitative account of chemical concepts, such as chemical cohesion, it fails at the quantitative level, because essential factors are ignored. The most important factor is the environment. The free atom of physics represents a universe, completely empty, except for a solitary atom. Such an atom can never explain chemical effects, which occur because of the interaction of an atom with its environment. When the total environment is taken into account one deals with the familiar classical macro world. Between the two extremes is chemistry and it is important to know whether to describe chemical entities, like molecules, in classical or non-classical terms. 

This problem relates to the question of where the so-called classical/quantum limit occurs. It has already been shown that Schrodinger s equation  

The left-hand side is a function of time only and the r.h.s. of coordinates only. This is only possible when both sides are equal to the same separation constant, E. Thus 

2m 2mA which has a form close to the Hamilton-Jacobi equation that describes the action (trajectory) of a classical system by  

---

When labeled polypeptides traveling down the axon are analyzed by SDS polyacrylamide gel electrophoresis, materials traveling in the axon can be grouped into five distinct rate components [6], Each rate component is characterized by a unique set of polypeptides moving coherently down the axon (Fig. 28-3). As specific polypeptides associated with each rate class were identified, most were seen to move only within a single rate component. Moreover, proteins that have common functions or interact with each other tend to be moved together. These observations led to a new view of axonal transport, the structural hypothesis [7]. This model can be stated simply proteins and other molecules move down the axon as component parts of discrete subcellular structures rather than as individual molecules (Table 28-1). 

The structural hypothesis, which was formulated in response to observations that axonal transport rate components move as discrete waves, each with a characteristic rate and a distinctive composition, can explain the coherent transport of functionally related proteins and is consistent with the relatively small numbers of motor molecules in neurons. The only assumption is that the number of elements that can interact with transport motor complexes is limited, and this requires appropriate packaging of the transported material. Different rate components result from packaging of transported material into different, cytologically identifiable, structures. In fact, the faster rates reflect the transport of proteins preassembled as membranous organelles, including vesicles and... 

FIGURE 28-3 Two-dimensional fluorographs showing the 35S methionine-labeled polypeptides in the three major anterograde rate components of axonal transport SCa, slow component a SCb, slow component b FC, fast component. Note that rate component not only has a characteristic rate but a characteristic polypeptide composition. The discovery that each rate component has a different polypeptide composition led to the structural hypothesis. (With permission from Tytell, M. etal. SciencellA 179-181, 1981 [6] illustration provided by Dr. Michael Tytell.)... 

FIGURE 28-5 Schematic illustration of the movement of cytoskeletal elements in slow axonal transport. Slow axonal transport represents the movement of cytoplasmic constituents including cytoskeletal elements and soluble enzymes of intermediary metabolism at rates of 0.2-2 mm/day which are at least two orders of magnitude slower than those observed in fast axonal transport. As proposed in the structural hypothesis and supported by experimental evidence, cytoskeletal components are believed to be transported down the axon in their polymeric forms, not as individual subunit polypeptides. Cytoskeletal polypeptides are translated on cytoplasmic polysomes and then are assembled into polymers prior to transport down the axon in the anterograde direction. In contrast to fast axonal transport, no constituents of slow transport appear to be transported in the retrograde direction. Although the polypeptide composition of slow axonal transport has been extensively characterized, the motor molecule(s) responsible for the movement of these cytoplasmic constituents has not yet been identified. 

In favorable systems, the coherent movement of neuro-filaments and microtubule proteins provides strong evidence for the structural hypothesis. Striking evidence was provided by pulse-labeling experiments in which NF proteins moved over periods of weeks as a bell-shaped wave with little or no trailing of NF protein. Similarly, coordinated transport of tubulin and MAPs makes sense only if MTs are being moved, since MAPs do not interact with unpolymerized tubulin [31]. 

Lasek, R. J. and Brady, S. T. The Structural Hypothesis of axonal transport Two classes of moving elements. In D. G. Weiss (ed.), Axoplasmic Transport. Berlin Springer-Verlag, 1982, pp. 397-405. 

Another group of theories is based upon intermolecular strain dependent effects caused 1) by orientationally active short chains, 2) by excluded volume, and 3) by a structuring in the network, including entanglements. The first two do not yield a sufficiently large C2. For the third, several proposals have been made, but they are either qualitative or, as yet, incomplete. The structuring hypothesis needs special emphasis because we have seen that many networks may indeed exhibit much more structure than is implied by the normal picture of coiling-chain networks. 

One of the most classic examples of chiral expression in thermotropic liquid crystals is that of the stereospecific formation of helical fibres by di-astereomers of tartaric acid derivatised either with uracil or 2,6-diacylamino pyridine (Fig. 9) [88]. Upon mixing the complementary components, which are not liquid crystals in their pure state, mesophases form which exist over very broad temperature ranges, whose magnitude depend on whether the tartaric acid core is either d, l or meso [89]. Electron microscopy studies of samples deposited from chloroform solutions showed that aggregates formed by combination of the meso compounds gave no discernable texture, while those formed by combinations of the d or l components produced fibres of a determined handedness [90]. The observation of these fibres and their dimensions makes it possible that the structural hypothesis drawn schematically in Fig. 9 is valid. This example shows elegantly the transfer of chirality from the molecular to the supramolecular level in the nanometer to micrometer regime. 

The synthesis of the library proceeded smoothly as planned, and only two purifications were necessary. The four intermediates 8.20 were chromatographed and the final, basic library individuals were purified by ion-exchange chromatography, both steps being amenable to automation for synthesis of a larger library. The library LI validated the chemical route and confirmed the structural hypothesis of 1,3-hy-droxyamine-containing carbohydrate scaffolds as RNA binders. The compounds were tested and showed RNA-binding activity, even if the desired sequence specificity was not observed (54). 

The intermediate expected to be formed upon protonation of 1,1-diphenyl-ethylene anion radical is [4 R = phenyl]. An LSV study has confirmed the structural hypothesis (Lerflaten and Parker, 1982a). Protonation by methanol... 

Bleijenberg, K. C. Luminescence Properties of Uranate Centres in Solids. Vol, 42, pp. 97-128. Boeyens, J. C. A. Molecular Mechanics and the Structure Hypothesis. Vol. 63, pp. 65-101. Bonnelle, C. Band and Localized States in Metallic Thorium, Uranium and Plutonium, and in... 

Molecular structure makes no appearance in a quantum treatment of molecules starting from first principles. We are thus dealing with a qualitative change in the theory which is expressed in the mathematics by a discontinuous approximation, and one is bound to question whether invoking the structure hypothesis is always the right thing to do. (Woolley, 1978, p. 1076)... 

In the zero approximation the electrolyte solution is treated as a mixture of ideal noninteracting ions. The fact that this approximation gives good results when applied to a dilute solution of, for example, NaCl is strong evidence for the structural hypothesis that NaCl dissociates into Na and Cl" ions in solution. 

Boeyens, J. C. A. Molecular mechanisms and the structure hypothesis. Struct. Bond. (Berlin) 1985, 63, 85. 

As to the structural hypothesis 109 (Kurasawa et al. 1985a, b), there can be several arguments not in its favor. First the 109 does not contain olefin fragments with the corresponding proton spin-system. Second, some of the calculated chemical shifts (CSs) deviate dramatically from those established experimentally. In particular, the C(3) (50 ppm) and the C(4) (146 ppm) which obviously disagree with experimental CSs (Mamedov et al. 2014a, b). 

---