Evidence from mixed hydrate nucleation for a funnel model of crystallization

Abstract

The molecular-level details of crystallization remain unclear for many systems. Previous work has speculated on the phenomenological similarities between molecular crystallization and protein folding. Here we demonstrate that molecular crystallization can involve funnel-shaped potential energy landscapes through a detailed analysis of mixed gas hydrate nucleation, a prototypical multicomponent crystallization process. Through this, we contribute both: (i) a powerful conceptual framework for exploring and rationalizing molecular crystallization, and (ii) an explanation of phenomenological similarities between protein folding and crystallization. Such funnel-shaped potential energy landscapes may be typical of broad classes of molecular ordering processes, and can provide a new perspective for both studying and understanding these processes. nucleation | gas clathrate hydrates | potential energy landscapes | crystallization funnel | molecular dynamics simulation M olecular crystallization and its inhibition are important to a broad range of fields. For example, some organisms [such as Antarctic fish (1) and winter rye (2)] have developed a rich chemistry of antifreeze proteins to control internal freezing, and there is significant interest in exploiting antifreeze proteins for food applications (e.g., see ref.3). Gas hydrate formation in oil and gas pipelines is a major industrial concern (4). For pharmaceuticals, there is much interest in understanding and controlling crystal polymorphism (e.g., see ref. 5). A better understanding of molecular crystallization, and factors influencing these processes, has potential to aid further advancements in such fields. As highlighted by a recent review on crystallization (6), traditional theoretical models of crystallization (e.g., classical nucleation theory) have proven to be problematic for a variety of systems and there remain technical challenges to studying crystallization both experimentally and computationally, so a clear understanding of crystal nucleation has yet to emerge.Molecular crystallization is one of the major classes of molecular ordering processes. Other molecular ordering processes include micelle formation, the formation of coordination polymers, and protein folding. Previous work has asserted, although not substantiated, that crystallization and protein folding are somehow similar processes. For example, protein folding has been speculatively described as a first-order phase transition similar to liquidsolid transitions (7). It has also been proposed that both the waterice transition and protein folding are difficult to study in silico because both are complex searches for relatively few ordered structures among numerous disordered alternative structures (8). The aim of this study is twofold: (i) to provide a conceptual description of molecular crystallization (simply referred to as crystallization henceforth), and (ii) to provide an explanation of the apparent similarities between crystallization and protein folding. On the basis of extensive simulati...

Does Local Structure Bias How a Crystal Nucleus Evolves?

“…37 Previous work has demonstrated that these cages are important to the early-stage formation of CH4, H2S, and mixed CH4/H2S hydrates. [38][39][40][41][42][43] As can be seen in Fig Fig. 3A to Fig.…”

“…These structurally-biased dynamics are consistent with recent work probing the rugged funnel-shaped potential-energy landscapes associated with crystal nucleation. 43 During nucleation in a liquid, a system progresses from an initial high-energy, highentropy liquid state (i.e., the broad mouth of the funnel) to a low-energy, low-entropy crystalline state (i.e., its narrow bottom). Since the landscape is locally rugged with local minima and maxima, the system must navigate according to its thermal energy as it descends further into the funnel.…”

“…This study's MD simulations used the following models: H2O was simulated using the TIP4P/2005 model; 56 H2S was represented using the Forester et al's four-site model 57 with the H-S bond distance set to 1.34 Å; and CH4 was represented using a Lennard-Jones model with ε = 1.22927 kJ/mol and σ = 3.700 Å as has been used by previous simulation-based hydrate studies. 43,58…”

Bridging solution properties to gas hydrate nucleation through guest dynamics

“…Correspondingly, the diffusion mechanism of guest molecules changes from more Brownian-like motion in the liquid phase to hopping-like behavior more consistent with a solid phase. 34,35 Using the funnel-shaped potential energy landscape for gas hydrate nucleation, 36 a system with high x g can be seen to approach the narrow neck region of its funnel-shaped energy landscape so that water cages can readily form and trigger hydrate nucleation. Addressing the question of ice nucleation is apparently more difficult than for gas hydrates at comparable undercooling, 36 the present results confirm that the presence of guest molecules in water does decrease the system entropy, and accordingly, the configurational space of the system (on its funnel-shaped energy landscape) is narrowed, so the system can more readily find a pathway to the solid phase.…”

Molecular properties of interfaces relevant for clathrate hydrate agglomeration

“…Multiple groups have studied hydrate formation with varying molecular models, ensembles and thermodynamic conditions [25]. The results from brute force simulations suggest hydrate formation occurs via a cooperative adsorption and growth mechanism between guest and host, and (despite some variability in resulting crystallinity) that the resulting post-critical solid structure at high driving force is generally amorphous while the resulting solid structure at lower driving forces is more crystalline, suggesting multiple drivingforce-dependent pathways [26][27][28][29][30][31]. Alternative methods to the brute force technique include the Forward Flux method [32], and metadynamics with restrained MD [33], employed by Lauricella et al, who suggested the main "pre-simulation" theories for the hydrate nucleation mechanism may all occur.…”